Acetic Acid → HCID 86638161, compound

HRID 423432Notes

Reaction equation

HRID 423432 reaction equation
[C:1]([BH3-])#N.[Na+].Cl.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:38][C:16]3[C:17](=[O:37])[N:18]([C:21]4[CH:22]=[N:23][C:24]([N:27]5[CH2:31][CH2:30][C@@H:29]([NH:32][CH2:33][CH:34]([F:36])[F:35])[CH2:28]5)=[CH:25][CH:26]=4)[CH:19]=[CH:20][C:15]=3[CH:14]=2)=[CH:9][CH:8]=1.C(O)(=O)C.C=O>CO>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[S:38][C:16]3[C:17](=[O:37])[N:18]([C:21]4[CH:22]=[N:23][C:24]([N:27]5[CH2:31][CH2:30][C@@H:29]([N:32]([CH2:33][CH:34]([F:36])[F:35])[CH3:1])[CH2:28]5)=[CH:25][CH:26]=4)[CH:19]=[CH:20][C:15]=3[CH:14]=2)=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24759459HCID 24759459, compound

Product 1

HCID 86638161HCID 86638161, compoundYield 80.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

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. concentrationConcentrate the mixture
  2. custompartition between CH2Cl2 (5 mL) and 1N NaOH (5 mL)
  3. customSeparate the organic portion
  4. extractionextract the aqueous portion with CH2Cl2 (3×)
  5. dry with materialDry the combined organics over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate to dryness
  8. customPurify by chromatography 0% to 5% MeOH (2M NH3)/CH2Cl2

Sources & evidence

ORD record
ord-42a575fd82a14919bc628184e5ea63f5
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

Loading…