Trifluoroacetic acid → 3-(1,3-Benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine

HRID 908385ノート

反応式

HRID 908385 の反応式
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[C:9]([CH3:26])=[N:10][N:11]([CH:13]3[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]3)[CH:12]=2)=[CH:4][C:3]=1[C:27]1[O:28][C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=1.C(O)(C(F)(F)F)=O>ClCCl.C(#N)C>[O:28]1[C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[N:31]=[C:27]1[C:3]1[C:2]([NH2:1])=[N:7][CH:6]=[C:5]([C:8]2[C:9]([CH3:26])=[N:10][N:11]([CH:13]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)[CH:12]=2)[CH:4]=1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 57687030Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate

生成物 1

HCID 425993613-(1,3-Benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine収率 73.5%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

To a solution of tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-methyl-pyrazol-1-yl]piperidine-1-carboxylate (500 mg) in dichloromethane (3 ml) was added TFA (1 ml). The solution was stirred at 25° C. for 2 hours. The mixture was evaporated to dryness, then the residue was diluted in dichloromethane and ammonia in methanol 7N was added. After removal of solvents, the crude product was purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane followed by 10 to 25% methanolic ammonia (7 N) in dichloromethane. The solvent was evaporated to dryness to afford a solid which was stirred in acetonitrile overnight, filtered and dried to afford 3-(1,3-benzoxazol-2-yl)-5-[3-methyl-1-(4-piperidyl)pyrazol-4-yl]pyridin-2-amine (290 mg) as a solid; NMR Spectrum: (DMSOd6) 1.77 (dd, 1H), 1.82 (dd, 1H), 1.93-1.99 (m, 2H), 2.12 (bs, 1H), 2.32 (s, 3H), 2.58 (ddd, 1H), 3.01-3.07 (m, 2H), 4.06-4.25 (m, 1H), 7.41-7.48 (m, 2H), 7.64 (bs, 2H), 7.80 (dd, 1H), 7.84 (dd, 1H), 8.04 (s, 1H), 8.28 (d, 1H), 8.35 (d, 1H); Mass spectrum: M+H+: 375

後処理

  1. customThe mixture was evaporated to dryness
  2. additionthe residue was diluted in dichloromethane
  3. additionammonia in methanol 7N was added
  4. customAfter removal of solvents
  5. customthe crude product was purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane
  6. customThe solvent was evaporated to dryness
  7. customto afford a solid which
  8. filtrationfiltered
  9. customdried

出典と根拠

ORDレコード
ord-3a8112e9197f46398b657f7450d740f2
出典データセット
uspto-grants-2011_09
特許番号
US08017611B2

反応ノート

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