Acetic Acid → Ammonia methanol

HRID 1716943Notes

Reaction equation

HRID 1716943 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:19])[C:10]2[C:15]([F:16])=[CH:14][C:13]([F:17])=[CH:12][C:11]=2[F:18])[CH:5]=[CH:4][CH:3]=1.[CH3:20][N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CN1CCCCC1=O.C(N)(=O)C1C=CC=CC=1.C(Cl)[Cl:64]>ClCCCl>[NH3:1].[CH3:9][OH:19].[ClH:64].[ClH:64].[F:16][C:15]1[CH:14]=[C:13]([F:17])[CH:12]=[C:11]([F:18])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][CH:3]=[C:2]([NH:1][CH:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[N:7]=1)=[O:19]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 2331BenzamideHCID 6344DichloromethaneHCID 13603N-Methyl-2-piperidoneHCID 740491-Methyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydride2×HCID 58997339HCID 58997339, compound

Product 2

HCID 21705897Ammonia methanolYield 4%HCID 66939247HCID 66939247, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Combine N-(6-amino-pyridin-2-yl)-2,4,6-trifluoro-benzamide (Preparation 43, 668 mg, 2.5 mmol), 1-methyl-4-piperidone (566 mg, 5.0 mmol), acetic acid (450 mg, 0.43 mL, 7.5 mmol), molecular sieves 4 A (1 g) and 1,2-dichloroethane, stir for 30 min at room temperature, then add sodium triacetoxyborohydride (1.325 g, 6.25 mmol) portion wise. Add another batch of 1-methyl-piperidone (566 mg, 5.0 mmol) and sodium triacetoxyborohydride (1.325 g, 6.25 mmol) if starting benzamide is still present after overnight reaction. Quench the reaction with 0.1N NaOH solution. Extract the mixture with ethylacetate three times. Combine organic layers, dry over Na2SO4, filter and concentrate to afford a residue. Chromatography (silica gel, 4% 2M NH3-methanol in CH2Cl2) provides 571 mg (63%) of the free base of the title compound. Dilute the free base in CH2Cl2 (1 mL), add 1M HCl/Et2O (5.6 mL, 5.6 mmol), remove the supernatant, wash the white solid with ether four times and dry in vacuum oven to afford 600 mg (88%) of the free base of the title compound. Using a salt formation method similar to that described in Example 53 gives the title compound: Free base: mass spectrum (ion spray): m/z 365.0 (M+1); 1H NMR (CDCl3, ppm): 8.50 (1H, s), 7.49 (m, 2H), 6.70 (m, 2H), 6.14 (d, 1H), 4.38 (d, 1H), 3.48 (m, 1H), 2.78 (m, 2H), 2.28 (s, 3H), 2.05 (m, 4H), 1.51 (m, 2H). Di-hydrochloride salt: Anal calc'd for C18H19F3N40-2HCL: C, 49.44; H, 4.84; N, 12.81. Found: C, 49.31; H, 4.96; N, 12.49.

Workup

  1. customreaction
  2. customQuench
  3. customthe reaction with 0.1N NaOH solution
  4. extractionExtract the mixture with ethylacetate three times
  5. dry with materialCombine organic layers, dry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto afford a residue

Sources & evidence

ORD record
ord-08436eb8a4ef40449eb86d68a6f4835e
Source dataset
uspto-grants-2010_09
Patent number
US07803813B2

Reaction notes

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