Hydrochloric Acid → HCID 131729413, compound

HRID 423433Notes

Reaction equation

HRID 423433 reaction equation
Cl.C(O)C.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:38][C:15]3[C:16](=[O:37])[N:17]([C:20]4[CH:21]=[N:22][C:23]([N:26]5[CH2:30][CH2:29][C@@H:28]([N:31]([CH2:33][CH:34]([F:36])[F:35])[CH3:32])[CH2:27]5)=[CH:24][CH:25]=4)[CH:18]=[CH:19][C:14]=3[CH:13]=2)=[CH:8][CH:7]=1>ClCCl.CCOCC>[ClH:5].[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:38][C:15]3[C:16](=[O:37])[N:17]([C:20]4[CH:21]=[N:22][C:23]([N:26]5[CH2:30][CH2:29][C@@H:28]([N:31]([CH2:33][CH:34]([F:36])[F:35])[CH3:32])[CH2:27]5)=[CH:24][CH:25]=4)[CH:18]=[CH:19][C:14]=3[CH:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 86638161HCID 86638161, compound

Product 1

HCID 131729413HCID 131729413, compoundYield 160.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

Add sodium cyanoborohydride (716 μmol, 45 mg) to a room temperature mixture of 2-(4-chloro-phenyl)-6-{6-[(R)-3-(2,2-difluoro-ethylamino)-pyrrolidin-1-yl]-pyridin-3-yl}-6H-thieno[2,3-c]pyridin-7-one, hydrochloride (150 mg, 287 μmol), acetic acid (49 μL, 360 μmol,) and formaldehyde (115 μL, 1.53 mmol, 37% aqueous solution) in methanol (9 mL) and stir the mixture for 18 h. Concentrate the mixture and partition between CH2Cl2 (5 mL) and 1N NaOH (5 mL). Separate the organic portion and extract the aqueous portion with CH2Cl2 (3×). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Purify by chromatography 0% to 5% MeOH (2M NH3)/CH2Cl2 to afford 116 mg (80%) of 2-(4-chloro-phenyl)-6-(6-{(R)-3-[(2,2-difluoro-ethyl)-methyl-amino]-pyrrolidin-1-yl}-pyridin-3-yl)-6H-thieno[2,3-c]pyridin-7-one. Add 1M hydrogen chloride in ethanol (232 μL, 232 μmol) to a solution of 2-(4-chloro-phenyl)-6-(6-{(R)-3-[(2,2-difluoro-ethyl)-methyl-amino]-pyrrolidin-1-yl}-pyridin-3-yl)-6H-thieno[2,3-c]pyridin-7-one (232 μmol, 116 mg) in dichloromethane (2 mL) and stir the mixture at room temperature for 5 min. Dilute the mixture with of Et2O (8 mL) and filter. Rinse the solid with Et2O (2×) and dry under vacuum at 80° C. to afford 100 mg (80%) of the title compound. LC-MS/ES m/z (35Cl) 501.0 [M+H]+.

Workup

  1. filtrationfilter
  2. washRinse the solid with Et2O (2×)
  3. customdry under vacuum at 80° C.

Sources & evidence

ORD record
ord-dba11abcbf734f2dbfff4d1df75b9ef9
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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