Potassium Carbonate → Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate

HRID 908398ノート

反応式

HRID 908398 の反応式
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:11]([NH2:25])=[N:12][CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1.Br[C:27]1[C:28]([CH:45]=[O:46])=[N:29][N:30]([CH:32]2[CH2:37][CH2:36][N:35]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH2:34][CH2:33]2)[CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:25][C:11]1[N:12]=[CH:13][C:14]([C:27]2[C:28]([CH:45]=[O:46])=[N:29][N:30]([CH:32]3[CH2:33][CH2:34][N:35]([C:38]([O:40][C:41]([CH3:42])([CH3:44])[CH3:43])=[O:39])[CH2:36][CH2:37]3)[CH:31]=2)=[CH:15][C:10]=1[C:2]1[O:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 673889123-(1,3-Benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 86630149Tert-butyl 4-(4-bromo-3-formyl-pyrazol-1-yl)piperidine-1-carboxylate

生成物 1

HCID 86630148Tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate収率 85.1%

試薬・触媒・溶媒 2

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6342Acetonitrile溶媒

実験手順

A suspension of 3-(1,3-benzoxazol-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.3 g), tert-butyl 4-(4-bromo-3-formyl-pyrazol-1-yl)piperidine-1-carboxylate (0.362 g), potassium carbonate (0.335 g) and tetrakis(triphenylphosphine) palladium (0.093 g) in degassed acetonitrile (50 mL) was stirred at reflux overnight. The resulting suspension was cooled to ambient temperature, filtered, washed with dichloromethane (3×20 ml) and the filtrate was concentrated. The crude product was purified by flash chromatography on silica gel eluting with 5 to 90% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford tert-butyl 4-[4-[6-amino-5-(1,3-benzoxazol-2-yl)-3-pyridyl]-3-formyl-pyrazol-1-yl]piperidine-1-carboxylate (0.370 g) as a solid. NMR Spectrum: (DMSOd6) 1.44 (s, 9H), 1.87 (dd, 1H), 1.92 (dd, 1H), 2.09-2.18 (m, 2H), 2.97 (bs, 2H), 4.04-4.16 (m, 2H), 4.52-4.61 (m, 1H), 7.41-7.49 (m, 2H), 7.80 (dd, 1H), 7.82 (bs, 2H), 7.85 (dd, 1H), 8.48 (s, 1H), 8.56 (d, 1H), 8.65 (d, 1H), 9.99 (s, 1H); Mass spectrum: M+H+ 489.

後処理

  1. temperatureat reflux overnight
  2. filtrationfiltered
  3. washwashed with dichloromethane (3×20 ml)
  4. concentrationthe filtrate was concentrated
  5. customThe crude product was purified by flash chromatography on silica gel eluting with 5 to 90% ethyl acetate in petroleum ether
  6. customThe solvent was evaporated to dryness

出典と根拠

ORDレコード
ord-b311ff4ab8524600adb17b9107eca4db
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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