Chloroacetyl chloride → (2R,5R)-4-{2-[6-(1,1-Difluoro-butyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475505Notes

Reaction equation

HRID 1475505 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][OH:15])[NH:11][CH2:10][C@H:9]1[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]([C:23]1[CH:24]=[C:25]2[NH:31][CH2:30][C:29]([CH3:33])([CH3:32])[C:26]2=[N:27][CH:28]=1)([F:22])[CH2:19][CH2:20][CH3:21].Cl[CH2:35][C:36](Cl)=[O:37].CCN(C(C)C)C(C)C>>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][OH:15])[N:11]([CH2:35][C:36]([N:31]2[C:25]3[C:26](=[N:27][CH:28]=[C:23]([C:18]([F:22])([F:17])[CH2:19][CH2:20][CH3:21])[CH:24]=3)[C:29]([CH3:32])([CH3:33])[CH2:30]2)=[O:37])[CH2:10][C@H:9]1[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 709805096-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridineHCID 71003242(2R,5R)-tert-Butyl 5-(hydroxymethyl)-2-methylpiperazine-1-carboxylate

Product 1

HCID 70980732(2R,5R)-4-{2-[6-(1,1-Difluoro-butyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl esterYield 60%

Procedure

Following methods similar to those described in Preparation 203 or General Procedure 5, starting from (2R,5R)-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.69 g, 3.0 mmol), 6-(1,1-difluoro-butyl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine, chloroacetyl chloride (185 μL, 2.3 mmol) and DIPEA (1.42 mL, 8.4 mmol), gave the title compound (0.61 g, 60%). MS: [M+H]+=511.

Workup

  1. customthose described in Preparation 203 or General Procedure 5

Sources & evidence

ORD record
ord-0b3d79ba6c564607829aaa9e02c0a9e8
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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