Methylamine → 1-[4-[4-[6-Amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(methylaminomethyl)pyrazol-1-yl]-1-piperidyl]ethanone

HRID 908479Notes

Reaction equation

HRID 908479 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH:14]=[C:13]([C:15]3[CH:16]=[N:17][C:18]([NH2:30])=[C:19]([C:21]4[O:22][C:23]5[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=5[N:25]=4)[CH:20]=3)[C:12]([CH:31]=O)=[N:11]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:33][NH2:34].[Na]>CO.ClCCl.ClCCl.CO>[NH2:30][C:18]1[N:17]=[CH:16][C:15]([C:13]2[C:12]([CH2:31][NH:34][CH3:33])=[N:11][N:10]([CH:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)[CH:14]=2)=[CH:20][C:19]=1[C:21]1[O:22][C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=1

Participants

7

Reactant 3

HCID 6329MethylamineHCID 5360545SodiumHCID 866301551-(1-Acetyl-4-piperidyl)-4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]pyrazole-3-carbaldehyde

Product 1

HCID 576870321-[4-[4-[6-Amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(methylaminomethyl)pyrazol-1-yl]-1-piperidyl]ethanoneYield 16.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

Over a period of 5 minutes, a solution of 1-(1-acetylpiperidin-4-yl)-4-(6-amino-5-(1,3-benzoxazol-2-yl)pyridin-3-yl)-1H-pyrazole-3-carbaldehyde (132 mg) in MeOH/dichloromethane (1:1) that had been cooled to 0° C., was added to a stirred solution of methylamine (0.153 ml, 0.31 mmol) dissolved in dichloromethane (6 ml) and methanol (6 ml). The resulting solution was stirred at 0° C. for 20 minutes. Sodium triacetoxyhydroborate (78 mg) was added at 0° C. to the mixture and stirred at 0° C. for 5 hours. The mixture was evaporated. A saturated solution of sodium bicarbonate was added and the mixture was extracted with methylene chloride, dried over magnesium sulphate, filtered and evaporated under reduced pression. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (5 micron silica, 19 mm diameter, 100 mm length) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions were evaporated to dryness, tritured with hot acetonitrile, filtered and dried under reduce pressure to afford 1-[4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-(methylaminomethyl)pyrazol-1-yl]-1-piperidyl]ethanone (23 mg) as a solid. NMR Spectrum: (CDCl3) 1.86-2.11 (m, 2H), 2.15 (s, 3H), 2.13-2.24 (m, 1H), 2.24-2.33 (m, 1H), 2.60 (s, 3H), 2.73-2.84 (m, 1H), 3.21-3.32 (m, 1H), 3.96 (s, 2H), 3.97-4.06 (m, 1H), 4.31-4.42 (m, 1H), 4.70-4.85 (m, 1H), 6.97 (bs, 2H), 7.32-7.41 (m, 2H), 7.54 (s, 1H), 7.57 (dd, 1H), 7.73 (dd, 1H), 8.32 (s, 1H), 8.42 (s, 1H); Mass spectrum: M+H+ 446;

Workup

  1. stirringstirred at 0° C. for 5 hours
  2. customThe mixture was evaporated
  3. additionA saturated solution of sodium bicarbonate was added
  4. extractionthe mixture was extracted with methylene chloride
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated under reduced pression
  8. customThe reaction mixture was purified by preparative HPLC
  9. customThe fractions were evaporated to dryness, tritured with hot acetonitrile
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-ddf98a7d2f7741d8b761f157834490c5
Source dataset
uspto-grants-2011_09
Patent number
US08017611B2

Reaction notes

Loading…