JPH0587062B2

JPH0587062B2 -

Info

Publication number: JPH0587062B2
Authority: JP; Japan
Prior art keywords: group; amino; naphthylmethyl; add; propionyl
Prior art date: 1987-09-29
Legal status : Expired - Lifetime

Application number

JP63236728A

Other languages

English (en)

Japanese (ja)

Other versions

JPH0262856A (ja

Inventor

Hajime Morishima

Takashi Koike

Masato Nakano

Shugo Atsumi

Seiichi Tanaka

Kenji Matsuyama

Current Assignee

MSD KK

Original Assignee

Banyu Phamaceutical Co Ltd

Priority date

1987-09-29

Filing date

1988-09-21

Publication date

1993-12-15

1988-09-02 Priority claimed from EP88114374A external-priority patent/EP0309766B1/fr

1988-09-21 Application filed by Banyu Phamaceutical Co Ltd filed Critical Banyu Phamaceutical Co Ltd

1988-09-21 Priority to JP63236728A priority Critical patent/JPH0262856A/ja

1990-03-02 Publication of JPH0262856A publication Critical patent/JPH0262856A/ja

1993-12-15 Publication of JPH0587062B2 publication Critical patent/JPH0587062B2/ja

Status Granted legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims description 199
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 178
-1 1-naphthylmethyl Chemical group 0.000 claims description 166
125000000217 alkyl group Chemical group 0.000 claims description 80
125000000623 heterocyclic group Chemical group 0.000 claims description 65
239000002253 acid Substances 0.000 claims description 50
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 50
150000003839 salts Chemical class 0.000 claims description 47
125000000753 cycloalkyl group Chemical group 0.000 claims description 43
125000004433 nitrogen atom Chemical group N* 0.000 claims description 36
229910052757 nitrogen Inorganic materials 0.000 claims description 24
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
125000004430 oxygen atom Chemical group O* 0.000 claims description 21
125000004434 sulfur atom Chemical group 0.000 claims description 20
ICICNJHEULTQLY-KRALYZGHSA-N (2s)-2-[[(2s)-2-(tert-butylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)C(C)(C)C)CCCC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 ICICNJHEULTQLY-KRALYZGHSA-N 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 19
125000005842 heteroatom Chemical group 0.000 claims description 15
125000002950 monocyclic group Chemical group 0.000 claims description 15
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000004414 alkyl thio group Chemical group 0.000 claims description 12
125000003277 amino group Chemical group 0.000 claims description 11
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
125000004423 acyloxy group Chemical group 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
125000005843 halogen group Chemical group 0.000 claims description 9
150000001413 amino acids Chemical class 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 5
125000002619 bicyclic group Chemical group 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
KZOGVMNRYWJRME-UHFFFAOYSA-N 1-amino-5-cyclohexyl-1-morpholin-4-ylpentane-2,3-diol Chemical compound C1COCCN1C(N)C(O)C(O)CCC1CCCCC1 KZOGVMNRYWJRME-UHFFFAOYSA-N 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
239000002220 antihypertensive agent Substances 0.000 claims description 4
125000004442 acylamino group Chemical group 0.000 claims description 3
125000002072 seryl group Chemical group 0.000 claims description 3
125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
LTICUUBGIZYYAU-CLZHSDMDSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(furan-2-ylmethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@@H](CC=1C2=CC=CC=C2C=CC=1)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)S(=O)(=O)CC1=CC=CO1 LTICUUBGIZYYAU-CLZHSDMDSA-N 0.000 claims description 2
WDTSFELOIFOXMS-RNPUFIIPSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-4-methyl-2-[[(2s)-2-(propan-2-ylsulfonylmethyl)-3-quinolin-8-ylpropanoyl]amino]pentanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=NC=CC=C2C=CC=1)CS(=O)(=O)C(C)C)CC(C)C)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 WDTSFELOIFOXMS-RNPUFIIPSA-N 0.000 claims description 2
WDXBQRUGPJZRKT-LJHWHBDJSA-N (2s)-2-[[(2s)-2-benzyl-3-(furan-2-ylmethylsulfonyl)propanoyl]amino]-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]hexanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)CS(=O)(=O)CC=1OC=CC=1)C1=CC=CC=C1 WDXBQRUGPJZRKT-LJHWHBDJSA-N 0.000 claims 1
MAXSDJUORSCIRM-LJHWHBDJSA-N (2s)-2-[[(2s)-2-benzyl-3-cyclopentylsulfonylpropanoyl]amino]-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-(4-oxidomorpholin-4-ium-4-yl)pentan-2-yl]hexanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)C[N+]1([O-])CCOCC1)CS(=O)(=O)C1CCCC1)C1=CC=CC=C1 MAXSDJUORSCIRM-LJHWHBDJSA-N 0.000 claims 1
IKZGESODNCALLW-GCIGRYLYSA-N (2s)-2-[[(2s)-2-benzyl-3-pyrimidin-2-ylsulfonylpropanoyl]amino]-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]hexanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)CS(=O)(=O)C=1N=CC=CN=1)C1=CC=CC=C1 IKZGESODNCALLW-GCIGRYLYSA-N 0.000 claims 1
SUIGKVKRDQITIT-BTWQBLKXSA-N (2s)-n-[(2s)-1-[[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanamide Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)C1=CN=CN1 SUIGKVKRDQITIT-BTWQBLKXSA-N 0.000 claims 1
LDMRAHMPQWKRIK-ITUQMYGTSA-N (2s)-n-[(2s)-1-[[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]amino]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]-2-(naphthalen-1-ylmethyl)-3-propan-2-ylsulfinylpropanamide Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)C(C)C)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)C1=CN=CN1 LDMRAHMPQWKRIK-ITUQMYGTSA-N 0.000 claims 1
BLBQAONVMIHHMA-DFRGSZQTSA-N (2s)-n-[(2s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C(CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)C(O)C(O)CN1CCOCC1)C1CCCCC1 BLBQAONVMIHHMA-DFRGSZQTSA-N 0.000 claims 1
NFTBZCHHUHQJRY-LPYGFTEJSA-N (2s)-n-[(2s)-1-cyclohexyl-5-[ethyl(2-hydroxyethyl)amino]-3,4-dihydroxypentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)C(O)C(O)CN(CC)CCO)C1CCCCC1 NFTBZCHHUHQJRY-LPYGFTEJSA-N 0.000 claims 1
WTMNFNLILAKIMY-KRALYZGHSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-(1-oxidopiperidin-1-ium-1-yl)pentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)C[N+]1([O-])CCCCC1)C1CCCCC1 WTMNFNLILAKIMY-KRALYZGHSA-N 0.000 claims 1
HMKKDXIKCDIFTD-HOQQKOLYSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-(2-hydroxyethylamino)pentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CNCCO)C1CCCCC1 HMKKDXIKCDIFTD-HOQQKOLYSA-N 0.000 claims 1
QWTXTVKRDMQQOT-LJHWHBDJSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-(2-methoxyethylamino)pentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CNCCOC)C1CCCCC1 QWTXTVKRDMQQOT-LJHWHBDJSA-N 0.000 claims 1
WWMGAEUQBJAZDY-VOLCAMQRSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-(4-methylpiperidin-1-yl)pentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN1CCC(C)CC1)C1CCCCC1 WWMGAEUQBJAZDY-VOLCAMQRSA-N 0.000 claims 1
SBSKVDFNWYHFQP-RERVPDENSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfinylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 SBSKVDFNWYHFQP-RERVPDENSA-N 0.000 claims 1
VTELBQOMIKBAQA-GCIGRYLYSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-(3-methylphenyl)propanoyl]amino]hexanamide Chemical compound C([C@@H](C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)CS(=O)(=O)CC)C1=CC=CC(C)=C1 VTELBQOMIKBAQA-GCIGRYLYSA-N 0.000 claims 1
DQZAUYUJOYXOQT-QQEJMDCYSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-(5,6,7,8-tetrahydronaphthalen-1-yl)propanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C=2CCCCC=2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 DQZAUYUJOYXOQT-QQEJMDCYSA-N 0.000 claims 1
AQZARKHGAHCNTN-LJHWHBDJSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]-4-methylsulfanylbutanamide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 AQZARKHGAHCNTN-LJHWHBDJSA-N 0.000 claims 1
SOHDKPLFSIXCCB-KAAJUZHGSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-quinolin-8-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=NC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 SOHDKPLFSIXCCB-KAAJUZHGSA-N 0.000 claims 1
QXKZVIIRXRCFPG-NTXHHJEXSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]-2-[[(2s)-2-(naphthalen-1-ylmethyl)-3-pyrimidin-2-ylpropanethioyl]amino]hexanamide Chemical compound C([C@@H](C(=S)N[C@@H](CCCC)C(=O)N[C@@H](CC1CCCCC1)[C@@H](O)[C@@H](O)CN1CCOCC1)CC=1C2=CC=CC=C2C=CC=1)C1=NC=CC=N1 QXKZVIIRXRCFPG-NTXHHJEXSA-N 0.000 claims 1
XGQLSOUSWAXTLW-KRALYZGHSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-piperidin-1-ylpentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN1CCCCC1)C1CCCCC1 XGQLSOUSWAXTLW-KRALYZGHSA-N 0.000 claims 1
NBSQXDTVPUCLPL-QQEJMDCYSA-N (2s)-n-[(2s,3r,4s)-1-cyclohexyl-5-(diethylamino)-3,4-dihydroxypentan-2-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)[C@@H](O)[C@@H](O)CN(CC)CC)C1CCCCC1 NBSQXDTVPUCLPL-QQEJMDCYSA-N 0.000 claims 1
BZEWYDLZRQIHCF-QMVABORWSA-N (2s)-n-[(2s,3r,4s)-2,3-dihydroxy-6-methyl-1-morpholin-4-ylheptan-4-yl]-2-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]hexanamide Chemical compound C([C@H](O)[C@H](O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)CCCC)N1CCOCC1 BZEWYDLZRQIHCF-QMVABORWSA-N 0.000 claims 1
RCGQGPNDOYXDOL-QQEJMDCYSA-N [(3s)-4-[[(2s,3r,4s)-1-cyclohexyl-3,4-dihydroxy-5-morpholin-4-ylpentan-2-yl]amino]-3-[[(2s)-2-(ethylsulfonylmethyl)-3-naphthalen-1-ylpropanoyl]amino]-4-oxobutyl] acetate Chemical compound C([C@H](NC(=O)[C@H](CCOC(C)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2C=CC=1)CS(=O)(=O)CC)[C@@H](O)[C@@H](O)CN1CCOCC1)C1CCCCC1 RCGQGPNDOYXDOL-QQEJMDCYSA-N 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 461
239000000243 solution Substances 0.000 description 255
238000003756 stirring Methods 0.000 description 254
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 244
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 214
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 212
230000002829 reductive effect Effects 0.000 description 184
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 176
239000002904 solvent Substances 0.000 description 174
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 150
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
238000006243 chemical reaction Methods 0.000 description 145
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 131
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 130
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 123
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 113
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 95
238000005481 NMR spectroscopy Methods 0.000 description 93
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 87
239000012230 colorless oil Substances 0.000 description 87
238000001035 drying Methods 0.000 description 80
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 78
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 74
238000010898 silica gel chromatography Methods 0.000 description 69
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 67
239000010410 layer Substances 0.000 description 67
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 66
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 65
238000000034 method Methods 0.000 description 62
LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 56
238000001819 mass spectrum Methods 0.000 description 53
239000007864 aqueous solution Substances 0.000 description 52
235000019441 ethanol Nutrition 0.000 description 51
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 46
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 46
239000000741 silica gel Substances 0.000 description 45
229910002027 silica gel Inorganic materials 0.000 description 45
239000007787 solid Substances 0.000 description 45
150000002148 esters Chemical class 0.000 description 44
238000005406 washing Methods 0.000 description 44
239000000843 powder Substances 0.000 description 41
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 39
229960000583 acetic acid Drugs 0.000 description 39
239000000284 extract Substances 0.000 description 39
235000011054 acetic acid Nutrition 0.000 description 36
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 35
239000012044 organic layer Substances 0.000 description 35
229920006395 saturated elastomer Polymers 0.000 description 35
CZROWHOGJRLBIE-QMMMGPOBSA-N tert-butyl (2s)-2-aminohexanoate Chemical compound CCCC[C@H](N)C(=O)OC(C)(C)C CZROWHOGJRLBIE-QMMMGPOBSA-N 0.000 description 35
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 31
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