Ammonium Chloride → HCID 131729412, compound

HRID 423424Notes

Reaction equation

HRID 423424 reaction equation
C([BH3-])#N.[Na+].[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:33][C:15]3[C:16](=[O:32])[N:17]([C:20]4[CH:21]=[N:22][C:23]([O:26][C@@H:27]5[CH2:31][CH2:30][NH:29][CH2:28]5)=[CH:24][CH:25]=4)[CH:18]=[CH:19][C:14]=3[CH:13]=2)=[CH:8][CH:7]=1.C(O[C:37]1(O[Si](C)(C)C)[CH2:39][CH2:38]1)C.[Cl-].[NH4+]>C(O)(=O)C.CO.ClCCl.ClCCl.CO>[ClH:5].[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[S:33][C:15]3[C:16](=[O:32])[N:17]([C:20]4[CH:21]=[N:22][C:23]([O:26][C@@H:27]5[CH2:31][CH2:30][N:29]([CH:37]6[CH2:39][CH2:38]6)[CH2:28]5)=[CH:24][CH:25]=4)[CH:18]=[CH:19][C:14]=3[CH:13]=2)=[CH:8][CH:7]=1

Participants

9

Reactant 4

HCID 25517Ammonium Chloride2×HCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 24758096HCID 24758096, compound

Product 1

HCID 131729412HCID 131729412, compoundYield 45.4%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
80 °C

Procedure

Add sodium cyanoborohydride (0.044 g, 0.703 mmol) to a mixture of 2-(4-chloro-phenyl)-6-[6-(pyrrolidin-3(R)-yloxy)-pyridin-3-yl]-6H-thieno[2,3-c]pyridin-7-one (0.0745 g, 0.176 mmol) and (1-ethoxy-cyclopropoxy)-trimethyl-silane (0.14 mL, 0.703 mmol) in acetic acid (0.05 mL) and methanol (10 mL) at room temperature. Reflux the mixture overnight at 80° C. Dilute the reaction mixture with dichloromethane and wash with 1.0M NaOH. Dilute the organic phase with methanol, dry over sodium sulfate, filter, and concentrate. Purify the mixture using silica gel flash column chromatography, eluting with 2-12% MeOH (2N NH3)/CH2Cl2. Triturate the residue with methanol to yield a white solid. Dissolve the white solid in dichloromethane/methanol, then add ammonium chloride (2 mg) and sonicate the resulting mixture until dissolution of the ammonium chloride. Concentrate the solution, then pump on high vacuum overnight to yield the desired product (0.020 g, 23%). MS/ES m/z (35Cl) 464.2 [M+H+].

Workup

  1. washwash with 1.0M NaOH
  2. additionDilute the organic phase with methanol
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the mixture
  7. washeluting with 2-12% MeOH (2N NH3)/CH2Cl2
  8. customTriturate the residue with methanol
  9. customto yield a white solid
  10. concentrationConcentrate the solution
  11. custompump on high vacuum overnight

Sources & evidence

ORD record
ord-1038fa4eadf94694b76e28e068c5e9f5
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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