Acetic Acid → Ammonium Hydroxide

HRID 1890719Notes

Reaction equation

HRID 1890719 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@:9]2([CH3:41])[CH2:14][NH:13][C:12]([CH3:16])([CH3:15])[C:11](=[O:17])[N:10]2[CH2:18][C:19]2[CH:20]=[N:21][C:22]3[C:27]([CH:28]=2)=[CH:26][C:25]2[CH2:29][C@:30]4([CH2:40][C:24]=2[CH:23]=3)[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[NH:32][C:31]4=[O:39])[CH:5]=[C:6]([F:8])[CH:7]=1.C=O.[CH3:44]C(O)=O.[BH3-]C#N.[Na+].[OH-].[Na+].C(N)CN>CO.C([O-])(O)=O.[Na+]>[NH4+:10].[OH-:17].[F:1][C:2]1[CH:3]=[C:4]([C:9]2([CH3:41])[CH2:14][N:13]([CH3:44])[C:12]([CH3:15])([CH3:16])[C:11](=[O:17])[N:10]2[CH2:18][C:19]2[CH:20]=[N:21][C:22]3[C:27]([CH:28]=2)=[CH:26][C:25]2[CH2:29][C@:30]4([CH2:40][C:24]=2[CH:23]=3)[C:38]2[C:33](=[N:34][CH:35]=[CH:36][CH:37]=2)[NH:32][C:31]4=[O:39])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 712FormaldehydeHCID 3301EthylenediamineHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 58550636HCID 58550636, compound

Product 2

HCID 14923Ammonium HydroxideHCID 50938859HCID 50938859, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent2×

Procedure

To a solution of (7S)-3-{[(2R)-2-(3,5-difluorophenyl)-2,5,5-trimethyl-6-oxopiperazin-1-yl]methyl}-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one, isomer B (15 mg, 0.027 mmol, described in Example 18), paraformaldehyde (8.1 mg, 0.27 mmol), and AcOH (0.0078 mL, 0.14 mmol) in MeOH (1 mL) was added NaCNBH3 (2.0 mg, 0.033 mmol). The reaction mixture was stirred for 16 h and then diluted with saturated aqueous NaHCO3 (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was dissolved in MeOH (1 mL). Sodium hydroxide (10 M, 0.014 mL, 0.14 mmol) and ethylenediamine (0.0037 mL, 0.054 mmol) were added and the solution was stirred for 30 min and then diluted with saturated aqueous NaHCO3 (5 mL) and extracted with CH2Cl2 (3×5 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:10:1, to give the title compound. MS: m/z=568 (M+1). HRMS: m/z=568.2520; calculated m/z=568.2519 for C33H32F2N5O2.

Workup

  1. extractionextracted with CH2Cl2 (3×10 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude product was dissolved in MeOH (1 mL)
  6. stirringthe solution was stirred for 30 min
  7. extractionextracted with CH2Cl2 (3×5 mL)
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel chromatography
  12. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-3bf912408f9f46b8b21f211a4f640c2d
Source dataset
uspto-grants-2013_08
Patent number
US08507477B2

Reaction notes

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