Potassium Iodide → (2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475521Notes

Reaction equation

HRID 1475521 reaction equation
Cl.Cl[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)[C:8]([CH3:24])([CH3:23])[CH2:7]1)=[O:5].[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[NH:35][CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.O>[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[N:35]([CH2:3][C:4]([N:6]2[C:14]3[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[CH:13]=3)[C:8]([CH3:24])([CH3:23])[CH2:7]2)=[O:5])[CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 70980298(2R,5S)-tert-butyl 2-methyl-5-(((R)-3-methylmorpholino)methyl)piperazine-1-carboxylateHCID 867240432-Chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride

Product 1

HCID 70980911(2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterYield 103.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

A mixture of 2-chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride (6.63 g, 17.96 mmol), (2R,5S)-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (5.62 g, 17.96 mmol), potassium carbonate (9.95 g, 72 mmol) and finely ground potassium iodide (5.98 g, 36 mmol) in acetonitrile (40 mL) was stirred at 20° C. for 1 h. Water (200 mL) was added and mixture stirred for 0.2 h, then the mixture was extracted with EtOAc (200 mL). The organic phase was dried (Na2SO4) and evaporated in vacuo to give the title compound (11.3 g) as an oil, used without further purification. 1H NMR (Me-d3-OD): 8.28-8.19 (1H, m), 8.13-8.04 (1H, m), 7.25 (2H, dd), 7.04 (2H, t), 4.23-4.13 (1H, m), 4.13-4.04 (2H, m), 4.04-3.95 (3H, m), 3.81-3.58 (4H, m), 3.54 (1H, d), 3.25 (2H, dd), 3.01-2.66 (4H, m), 2.62-2.42 (2H, m), 2.42-2.17 (2H, m), 1.47 (9H, s), 1.43-1.37 (6H, m), 1.29-1.21 (3H, m), 1.01 (3H, d). MS: [M+H]+=610. IR: vC═O 1685, 1653 cm−1.

Workup

  1. stirringmixture stirred for 0.2 h
  2. extractionthe mixture was extracted with EtOAc (200 mL)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated in vacuo

Sources & evidence

ORD record
ord-72b89d958b8d41faabd5f723063801ea
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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