Methyl acetoacetate → 5-(5-Chloro-2-fluoro-phenyl)-1-((S)-2,2-dimethyl-cyclopropylmethyl)-2-methyl-1H-pyrrole-3-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide

HRID 1593191Notes

Reaction equation

HRID 1593191 reaction equation
CO[C:3](=[O:8])[CH2:4][C:5](=O)[CH3:6].Br[CH2:10][C:11]([C:13]1[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=1[F:20])=O.[CH3:21][C:22]1([CH3:28])[CH2:24][C@@H:23]1[C:25]([NH2:27])=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].[NH2:35][C@@H:36]1[CH2:41][CH2:40][CH2:39][CH2:38][C@H:37]1[OH:42]>>[OH:42][C@@H:37]1[CH2:38][CH2:39][CH2:40][CH2:41][C@H:36]1[NH:35][C:3]([C:4]1[CH:10]=[C:11]([C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[F:20])[N:27]([CH2:25][C@H:23]2[CH2:24][C:22]2([CH3:28])[CH3:21])[C:5]=1[CH3:6])=[O:8]

Participants

6

Reactant 5

HCID 7757Methyl acetoacetateHCID 735777(1R,2R)-2-AminocyclohexanolHCID 10197657(S)-2,2-DimethylcyclopropanecarboxamideHCID 21226445Aluminium lithium hydrideHCID 790219212-Bromo-1-(5-chloro-2-fluorophenyl)ethanone

Product 1

HCID 589989125-(5-Chloro-2-fluoro-phenyl)-1-((S)-2,2-dimethyl-cyclopropylmethyl)-2-methyl-1H-pyrrole-3-carboxylic acid ((1R,2R)-2-hydroxy-cyclohexyl)-amide

Procedure

The title compound was synthesized in analogy to Example 68, using 3-oxo-butyric acid methyl ester as compound of formula R, 2-bromo-1-(5-chloro-2-fluoro-phenyl)-ethanone as compound of formula S, C—(S)-(2,2-dimethyl-cyclopropyl)-methylamine (prepared from (S)-2,2-dimethyl-cyclopropanecarboxylic acid amide by reduction with LiAlH4 according to the procedure described by Saski et al. J. Org. Chem. 1971, 36, 1968-1971) as R3—(CH2)m—NH2 and (1R,2R)-2-amino-cyclohexanol as R1R2NH, MS (ISP) 433.4 (M+H)+.

Sources & evidence

ORD record
ord-d485ae910a984ca698d25d90354e8ecb
Source dataset
uspto-grants-2007_11
Patent number
US07294644B2

Reaction notes

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