JP6212056B2 - Cf3o−含有エナミノケトンおよびcf3o−含有ピラゾールの調製のためのそれらの利用 - Google Patents
Cf3o−含有エナミノケトンおよびcf3o−含有ピラゾールの調製のためのそれらの利用 Download PDFInfo
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- JP6212056B2 JP6212056B2 JP2014557016A JP2014557016A JP6212056B2 JP 6212056 B2 JP6212056 B2 JP 6212056B2 JP 2014557016 A JP2014557016 A JP 2014557016A JP 2014557016 A JP2014557016 A JP 2014557016A JP 6212056 B2 JP6212056 B2 JP 6212056B2
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- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 1
- 238000009795 derivation Methods 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000012039 electrophile Substances 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- REPVNSJSTLRQEQ-UHFFFAOYSA-N n,n-dimethylacetamide;n,n-dimethylformamide Chemical compound CN(C)C=O.CN(C)C(C)=O REPVNSJSTLRQEQ-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- QHMQWEPBXSHHLH-UHFFFAOYSA-N sulfur tetrafluoride Chemical compound FS(F)(F)F QHMQWEPBXSHHLH-UHFFFAOYSA-N 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- WZCZNEGTXVXAAS-UHFFFAOYSA-N trifluoromethanol Chemical class OC(F)(F)F WZCZNEGTXVXAAS-UHFFFAOYSA-N 0.000 description 1
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 description 1
- GVZFDPPAJXHNGL-UHFFFAOYSA-N trifluoromethyl trifluoromethanesulfonate Chemical compound FC(F)(F)OS(=O)(=O)C(F)(F)F GVZFDPPAJXHNGL-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
- C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Furan Compounds (AREA)
Description
式中、
R1は、1から5個のハロゲン原子により置換されていてもよいC5−C10アリール、または酸素および窒素から選択される1個、2個もしくはそれより多いヘテロ原子を呈するC5−C10アリールであり、ならびに
R2およびR3は、独立して、C1−C6アルキル、C5−C10アリール、酸素および窒素から選択される1個、2個もしくはそれより多いヘテロ原子を呈するC5−C10アリールであるか、または5員もしくは7員環を共に形成する、エナミノケトンを調製する方法であって、
(A)式II
式中、R1は上で定義された通りであるCF3O−ケトンを
アミノホルミル化試薬と反応させること
を含む、前記方法に関する。
式IまたはII中のR1は、2−フリル、フェニルまたは1もしくは2個の塩素原子で置換されているフェニルであり、ならびに
式I中のR2およびR3は、独立して、C1−C6アルキルである。
式IまたはII中のR1は、2−フリル、フェニル、クロロフェニルまたはジクロロフェニルであり、ならびに
式I中のR2およびR3は、C1アルキルである。
式中、R4は上で定義された通りであるヒドラジンと反応させること
を含む、前記方法に関する。
式中、R4は水素でないという条件で、R4は上で定義された通りであるヒドラジンと反応させること
を含み、
前記(B)はメタノール、エタノールおよびトリフルオロエタノールよりなる群から選択される溶媒中で行われる、前記方法に関する。
式中、R4は上で定義された通りであるトリフルオロメトキシピラゾール酸を調製する方法であって、
式V−1の化合物であり、式中、R1は2−フリルであり、およびR4は上で定義された通りである化合物を酸化させることを含む、前記方法に関する。
本発明に関連して、用語ハロゲン(X)は、特に別の定義がない限り、フッ素、塩素、臭素およびヨウ素よりなる群から選ばれる元素を含み、フッ素、塩素および臭素が好ましく用いられ、フッ素および塩素がとりわけ好ましく用いられる。
微粉状のCuO(1.0当量)およびI2(1.0当量)を、よく撹拌された無水MeOH(C=0.25M)中のケトン溶液に加えた。混合物を5分間撹拌し、次いで還流させた。反応物の消失後(TLCによりモニターした)、混合物をろ過し、溶媒を減圧下で除去した。残渣を10% Na2S2O3溶液(10mL/mmolのケトン)中に注ぎ、混合物をAcOEtで抽出して(3×)、有機層を乾燥させた(Na2SO4)。溶媒を除去して残渣をカラムクロマトグラフィーにより精製することによって、目的生成物をもたらした(Synthesis 2007,3113−3116)。
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.63(dd,J=1.8/0.9Hz,1H)、7.32(dd,J=3.6/0.9Hz,1H)、6.58(dd,J=3.6/1.8Hz,1H)、4.24(s,2H)。13C NMR(75MHz,CDCl3):δ=181.9、149.6、146.9、118.8、112.8、0.6。
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.82(d,J=1.8Hz,2H)、7.55(dd,J=1.8/1.8Hz,1H)、4.34(s,3H)。13C NMR(75MHz,CDCl3):δ=190.2、139.1、135.7、135.6、133.2、127.2、0.9。
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.49(dd,J=8.1/1.5Hz,1H)、7.35(dd,J=7.5/1.5Hz,1H)、7.22(dd,J=8.1/7.5Hz,1H)、4.33(s,2H)。13C NMR(75MHz,CDCl3):δ=194.3、138.1、133.7、132.6、128.8、127.7、127.5、6.1。
ゴムのセプタムおよびマグネチックスターラーを備えた10mLの丸底フラスコの中に、AgF(1.1当量)を導入した。アルゴン雰囲気下、無水CH3CN(C=0.5M)を加え、不均一な混合物を−30℃まで冷却した。TFMT(1.1当量、300μL/mmolのヨードアセチル芳香族化合物を次いで加え、容器を密に閉め(COF2の自然圧(autogenous pressure)が反応を進行させるのに必要とされる)、反応混合物を2時間、−30℃で撹拌した。気密シリンジを使用して求電子剤(1.0当量、液体の場合は原液、または油もしくは固体の場合は最少量のCH3CN中に溶解させたもの)を添加した後、−30℃で30分間、次いで室温で24時間、撹拌を続けた(暗所において)。最後に、容器を減圧し、反応混合物をCelite(登録商標)でろ過した。ろ液を真空中で濃縮し、残渣をDCM中に溶解し、ブラインで洗浄し、MgSO4で乾燥させ、ろ過して真空中で濃縮した。シリカゲルに対するクロマトグラフィーによる精製は、最終的に、純粋な対応するトリフルオロメチルエーテルを与えた(J.Fluorine Chem.2010,131,200−207)。
黄色の油。1H NMR(300MHz,CDCl3):δ=7.91(m,2H);7.65(m,1H);7.52(m,2H);5.18(s,2H)。13C NMR:190.2;134.4;133.8;129.1;127.9;121.8(q,J=256.3);68.4(q,J=2.9)。19F NMR(282MHz,CDCl3):δ=−61.44(s,CF3)
1−(2−フリル)−2−(トリフルオロメトキシ)エタノン
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.63(dd,J=1.5/0.6Hz,1H)、7.35(dd,J=3.6/0.6Hz,1H)、6.61(dd,J=3.6/1.5Hz,1H)、5.01(s,2H)。13C NMR(75MHz,CDCl3):δ=179.4、150.1、147.2、121.6(q,1JC−F=255.0)、118.8、112.8、67.6(q,3JC−F=3.0)。19F NMR(282MHz,CDCl3):δ=−61.65(s)。
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.74(d,J=1.8Hz,2H)、7.59(dd,J=1.8/1.8Hz,1H)、5.12(s,3H)。13C NMR(75MHz,CDCl3):δ=188.1、136.1、135.9、133.9、127.3、126.3、121.5(q,1JC−F=255.6)、68.1(q,3JC−F=3.0)。19F NMR(282MHz,CDCl3):δ=−61.60(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.57(dd,J=8.1/1.8Hz,1H)、7.33(dd,J=7.5/1.8Hz,1H)、7.26(dd,J=8.1/7.5Hz,1H)、5.07(s,2H)。13C NMR(75MHz,CDCl3):δ=192.8、137.1、133.9、133.2、129.1、127.7、127.2、121.1(q,1JC−F=255.2)、69.7(q,3JC−F=2.9)。19F NMR(282MHz,CDCl3):δ=−61.28(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.82(dd,J=1.2/0.9Hz,1H)、7.73(ddd,J=7.8/1.5/1.2Hz,1H)、7.54(ddd,J=7.8/1.5/0.9Hz,1H)、7.40(dd,J=7.8/7.8Hz,1H)、5.14(s,2H)。13C NMR(75MHz,CDCl3):δ=188.9、135.2、135.0、134.0、130.2、127.8、125.8、121.4(q,1JC−F=255.1)、68.1(q,3JC−F=2.9)。19F NMR(282MHz,CDCl3):δ=−61.63(s)。
トリフルオロメトキシメチルアリールケトンまたはトリフルオロメトキシメチルヘテロアリールケトン(1.0当量)およびN,N−ジメチルホルムアミドジメチルアセタール(DMF.DMA)(10当量)の溶液を5時間還流させた(TLCによりモニターした)。反応混合物を冷却し、真空中で濃縮し、残渣をシリカゲルに対するクロマトグラフィーにより精製することで、純粋な所望のトリフルオロメトキシ化エナミノケトンが得られた。
黄色の油。1H NMR(300MHz,CDCl3):δ=7.60(m,2H);7.47−7.33(massif,3H);7.01(broad s,1H);3.12(s,6H)。13C NMR(75MHz,CDCl3):δ=188.5;145.4;139.4;130.6;128.4;128.2;122.9(m,);121.3(q,1JC−F=255.0);42.4(broad s)。19F NMR(282MHz,CDCl3):δ=−58.96(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.50(dd,J=1.5/0.6Hz,1H)、7.46(bs,1H)、7.10(dd,J=3.6/0.6Hz,1H)、6.61(dd,J=3.6/1.5Hz,1H)、3.12(s,6H)。13C NMR(75MHz,CDCl3):δ=173.9、151.6、144.8、143.5、121.3、121.1(q,1JC−F=255.0)、116.9、111.5、43.3、42.6。19F NMR(282MHz,CDCl3):δ=−59.47(s)。
黄色の固体(25℃で)。1H NMR(300MHz,CDCl3):δ=7.41(d,J=1.8Hz,2H)、7.36(dd,J=1.8/1.8Hz,1H)、7.01(bs,1H)、3.10(s,6H)。13C NMR(75MHz,CDCl3):δ=184.7、145.3、141.8、134.7、130.1、126.5、121.7、120.9(q,1JC−F=255.5)、30.7、29.1。19F NMR(282MHz,CDCl3):δ=−59.02(s)。
褐色の固体(25℃で)。1H NMR(300MHz,CDCl3):δ=7.47(d,J=8.1Hz,1H)、7.26(dd,J=8.1/7.5Hz,1H)、7.18(d,J=7.5Hz,1H)、6.56(bs,1H)、3.13(bs,6H)。13C NMR(75MHz,CDCl3):δ=183.2、147.0、140.2、132.9、130.4、128.7、126.4、125.7、122.3、120.6(q,1JC−F=255.4)、46.8、37.8。19F NMR(282MHz,CDCl3):δ=−58.74(s)。
褐色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.52(bs,1H)、7.41(ddd,J=7.5/1.8/1.2Hz,1H,)、7.35(ddd,J=7.8/1.8/0.9Hz,1H)、7.27(ddd,J=7.8/7.5/2.4Hz,1H)、6.96(bs,1H)、3.07(s,6H)。13C NMR(75MHz,CDCl3):δ=186.4、145.3(bs)、140.8、134.0、130.3、129.3、128.1、126.2、122.1(bs).121.0(q,1JC−F=255.1)、30.7。19F NMR(282MHz,CDCl3):δ=−59.25(s)。
氷AcOH(C=0.2M)中のトリフルオロメトキシ化エナミノケトン(1.0当量)の溶液に、ヒドラジン水和物(N2H4.H2O)(1.0当量)を加え、結果として得られた混合物を室温で一晩撹拌した。次いで、AcONa水溶液(5%)を加え、混合物をDCMで抽出した(3×)。有機層を合わせ、飽和NaHCO3、ブラインで洗浄し、MgSO4で乾燥させ、ろ過して真空中で濃縮した。シリカゲルに対するクロマトグラフィーによる精製は、最終的に、純粋なトリフルオロメトキシ化ピラゾールを与えた。
白色の固体(25℃で);Mp=84〜85℃;1H NMR(300MHz,CDCl3):δ=9.69(bs,1H)、7.73(m,2H)、7.62(bs,1H)、7.47−7.37(massif,3H);13C NMR(75MHz,CDCl3):δ=138.4(bs)、131.1(bs)、129.1、128.8、129.6(bs)、126.7、120.8(q,1JC−F=256.6);19F NMR(282MHz,CDCl3):δ=−60.77(s)。
オレンジ色の固体(25℃で)。Mp=85℃。1H NMR(300MHz,CDCl3):δ=11.45(bs,1H)、7.68(d,J=1.2Hz,1H)、7.51(dd,J=1.8/0.9Hz,1H)、6.80(dd,J=3.3/0.9Hz,1H)、6.56(dd,J=3.3/1.8Hz,1H)。13C NMR(75MHz,CDCl3):δ=144.1、142.2、132.2(bs)、129.3(bs)、124.9(bs)、120.8(q,1JC−F=252.2)、111.8、108.8。19F NMR(282MHz,CDCl3):δ=−61.00(s)。
白色の固体(25℃で)。Mp=89℃。1H NMR(300MHz,CDCl3):δ=11.56(bs,1H)、7.68(bs,1H)、7.61(d,J=1.8Hz,2H)、7.36(dd,J=1.8/1.8Hz,1H)。13C NMR(75MHz,CDCl3):δ=137.8(bs)、135.6、132.0、131.9(bs)、128.7、125.0、124.9(bs)、120.5(q,1JC−F=257.6)。19F NMR(282MHz,CDCl3):δ=−60.92(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=11.13(bs,1H)、7.59(bs,1H)、7.51(dd,J=7.5/1.8Hz,1H)、7.28(dd,J=7.8/1.8Hz,1H)、7.22(dd,J=7.8/7.5Hz,1H)。13C NMR(75MHz,CDCl3):δ=137.1(bs)、133.9、132.0、131.3、129.8(bs)、129.7、127.2、125.0(bs)、120.4(q,1JC−F=256.7)。19F NMR(282MHz,CDCl3):δ=−60.97(s)。
黄色の固体(25℃で)。Mp=44℃。1H NMR(300MHz,CDCl3):δ=12.20(bs,1H)、7.63(bs,1H)、7.54(bs,1H)、7.51(dd,J=7.8/1.8Hz,1H)、7.26(dd,J=7.8/1.8Hz,1H)、7.24(dd,J=7.8/7.8Hz,1H)。13C NMR(75MHz,CDCl3):δ=137.8、134.8、130.9(bs)、130.5、130.1、128.9、126.5、125.7(bs)、124.7、120.6(q,1JC−F=257.0)。19F NMR(282MHz,CDCl3):δ=−61.10(s)。
純粋なEtOH(C=0.2M)中のトリフルオロメトキシ化エナミノケトン(1.0当量)の溶液にメチルヒドラジン(MeNHNH2)(5.0当量)を加え、結果として得られた混合物を室温で5時間撹拌した(TLCによりモニターした)。次いで、反応混合物を真空中で濃縮し、残渣をAcOEt中に溶解し、水およびブラインで洗浄し、Na2SO4で乾燥させ、ろ過して真空中で濃縮した。シリカゲルに対するクロマトグラフィーによる精製は、最終的に、純粋なトリフルオロメトキシ化メチルピラゾールを与えた。
無色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.48(dd,J=1.8/0.9Hz,1H)、7.40(d,J=0.9Hz,1H)、6.70(dd,J=3.3/0.9Hz,1H)、6.47(dd,J=3.3/1.8Hz,1H)、3.90(s,3H)。13C NMR(75MHz,CDCl3):δ=145.2、142.2、135.0、129.1(bs)、122.6、120.6(q,1JC−F=256.0)、111.1、108.1、40.0。19F NMR(282MHz,CDCl3):δ=−61.08(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.72(d,J=1.8Hz,2H)、7.43(d,J=1.2Hz,1H)、7.30(dd,J=1.8/1.8Hz,1H)、3.88(s,3H)。13C NMR(75MHz,CDCl3):δ=138.8、135.1、133.7、130.7(q,3JC−F=2.4)、127.8、124.6、123.0、120.5(q,1JC−F=257.0)、40.0。19F NMR(282MHz,CDCl3):δ=−61.20(s)。
白色の固体(25℃で)。Mp=62℃。1H NMR(300MHz,CDCl3):δ=7.51(dd,J=7.8/1.5Hz,1H)、7.47(bs,1H)、7.33(dd,J=7.8/1.8Hz,1H)、7.24(dd,J=7.8/7.8Hz,1H)、3.93(s,1H)。13C NMR(75MHz,CDCl3):δ=140.8(bs)、133.5、132.3、132.0、131.1(bs)、130.7、130.0、127.0、122.1、120.4(q,1JC−F=254.8)、40.0。19F NMR(282MHz,CDCl3):δ=−61.12(s)。
黄色の油(25℃で)。1H NMR(300MHz,CDCl3):δ=7.83(bs,1H)、7.69(ddd,J=6.9/1.8/1.2Hz,1H)、7.36(d,J=1.2Hz,1H)、7.29(dd,J=7.5/6.9Hz,1H)、7.27(dd,J=7.5/1.8Hz,1H)、3.80。13C NMR(75MHz,CDCl3):δ=140.0、134.4、132.6、130.5(q,3JC−F=2.4)、129.7、127.9、126.3、124.4、122.9(bs)、120.5(q,1JC−F=256.4)、39.7。19F NMR(282MHz,CDCl3):δ=−61.25(s)。
n−ヘキサン/AcOEt/H2Oの混合物(1:1:2、C=0.1M)中の(2−フリル)−ピラゾール(1.0当量)の溶液にNaIO4(10当量)(これは、添加前にH2O中に予め溶解させることができる)を、その後にRuCl3(0.05M水溶液)(0.05当量)を加えた。不均一な反応混合物を室温で一晩、勢いよく撹拌した。次いで、混合物を固体NaCl(4g/mmolの複素環)および最少量の水の中に注いだ。10分間勢いよく撹拌した後、反応混合物をAcOEtで抽出した(×3)(合わせた水層のpH=3〜4)。有機層を合わせ、MgSO4で乾燥させ、ろ過して真空中で濃縮することで、粗精製の所望のカルボン酸をもたらした。反応はまた、(2−フリル)−ピリジンまたは(2−フリル)−ピリミジンを使用して行ってもよい。
白色の固体(25℃で)。1H NMR(300MHz,(CD3)2CO):δ=10.66(bs,1H)、7.94(d,J=0.9Hz,1H)。13C NMR(75MHz,(CD3)2CO):δ=160.4、134.6(bs)、131.2、128.0、121.4(q,1JC−F=254.6)。19F NMR(282MHz,(CD3)2CO):δ=−61.70(s)。
白色の固体(25℃で)。1H NMR(300MHz,(CD3)2CO):δ=10.76(bs,1H)、7.98(s,1H)、3.98(s,3H)。13C NMR(75MHz,(CD3)2CO):δ=161.3、134.7、134.1(q,3JC−F=2.7)、125.6、121.3(q,1JC−F=254.5)、40.7。19F NMR(282MHz,(CD3)2CO):δ=−61.86(s)。
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