Diisopropylethylamine → (S)-2-{[(1S,4S)-2-{(S)-1-[((S)-Cyclohexyl-methoxycarbonyl-methyl)-carbamoyl]-2-methyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopent-2-enecarbonyl]-amino}-pentanoic acid tert-butyl ester

HRID 2242421Notes

Reaction equation

HRID 2242421 reaction equation
[C:1]([O:5][C:6]([C@@H:8]([NH:12][C:13]([CH:15]1[C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=3)[N:27]=[C:26]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:25]=2)[CH2:16]1)=[O:14])[CH2:9][CH2:10][CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:42][O:43][C:44](=[O:60])[CH:45]([NH:52][C:53](=[O:59])[CH:54]([NH2:58])[CH:55]([CH3:57])[CH3:56])[CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CO.C1(C)C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[C@@H:8]([NH:12][C:13]([C@H:15]1[CH2:16][C@H:17]([O:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=3)[N:27]=[C:26]([C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:25]=2)[CH:18]=[C:19]1[C:20](=[O:22])[NH:58][C@H:54]([C:53](=[O:59])[NH:52][C@@H:45]([CH:46]1[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51]1)[C:44]([O:43][CH3:42])=[O:60])[CH:55]([CH3:57])[CH3:56])=[O:14])[CH2:9][CH2:10][CH3:11])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59204172HCID 59204172, compoundHCID 68490522(2-Amino-3-methyl-butyrylamino)-cyclohexyl-acetic acid methyl ester

Product 1

HCID 11468492(S)-2-{[(1S,4S)-2-{(S)-1-[((S)-Cyclohexyl-methoxycarbonyl-methyl)-carbamoyl]-2-methyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopent-2-enecarbonyl]-amino}-pentanoic acid tert-butyl esterYield 7.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

The acid 11 (0.051 g, 0.087 mmol) and (2-amino-3-methyl-butyrylamino)-cyclohexyl-acetic acid methyl ester (0.054 g, 0.21 mmol) were dissolved in DMF (1.5 mL) and cooled in an ice-bath. DIPEA (16 mg, 0.12 mmol) and HATU (47 mg, 0.13 mmol) were added. After two and a half hours the mixture was co-concentrated with toluene and methanol and then purified by flash column chromatography (toluene/ethyl acetate 3:1). Further purification was performed on HPLC (90% MeOH+0.2% TEA). This gave after co-concentration the two diastereomers 19a (9.4 mg, 13%) and 19b (5.3 mg, 7%) as slightly yellow syrups. After lyophilisation 19a and 19b were collected as white powders:

Workup

  1. temperaturecooled in an ice-bath
  2. custompurified by flash column chromatography (toluene/ethyl acetate 3:1)
  3. customFurther purification

Sources & evidence

ORD record
ord-ccb28e3207854bdd855bd8f711b60cd2
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

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