Carbon Tetrachloride → (R)-N,N-dimethyl-2-(4-(1-(thiazol-4-ylmethyl)-1H-indazol-5-ylamino)quinazolin-5-yloxy)propanamide

HRID 1162228ノート

反応式

HRID 1162228 の反応式
[CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9](=O)[NH:10][CH:11]=[N:12]2)[CH3:5].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl.[S:44]1[CH:48]=[C:47]([CH2:49][N:50]2[C:58]3[C:53](=[CH:54][C:55]([NH2:59])=[CH:56][CH:57]=3)[CH:52]=[N:51]2)[N:46]=[CH:45]1>ClCCCl>[CH3:1][N:2]([CH3:19])[C:3](=[O:18])[C@H:4]([O:6][C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[C:9]([NH:59][C:55]1[CH:54]=[C:53]3[C:58](=[CH:57][CH:56]=1)[N:50]([CH2:49][C:47]1[N:46]=[CH:45][S:44][CH:48]=1)[N:51]=[CH:52]3)=[N:10][CH:11]=[N:12]2)[CH3:5]

参加物

6

反応物 4

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 686176261-[(1,3-Thiazol-4-yl)methyl]-1H-indazol-5-amineHCID 136346624(2R)-N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide

生成物 1

HCID 16117347(R)-N,N-dimethyl-2-(4-(1-(thiazol-4-ylmethyl)-1H-indazol-5-ylamino)quinazolin-5-yloxy)propanamide収率 60%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

反応条件

温度
45 °C

実験手順

A mixture of (2R)—N,N-dimethyl-2-[(4-oxo-3,4-dihydroquinazolin-5-yl)oxy]propanamide (200 mg, 0.77 mmol), triphenylphosphine (603 mg, 2.3 mmol) and carbon tetrachloride (2.2 ml, 23 mmol) in 1,2-dichloroethane (5 ml) was stirred at 45° C. for 2 hours. 1-(1,3-Thiazol-4-ylmethyl)-1H-indazol-5-amine (184 mg, 0.8 mmol) was added and the solvents were evaporated under vacuum. Acetonitrile (5 ml) was added. The mixture was stirred at 75° C. for 2 hours. After cooling, the solvents were evaporated under vacuum. The residue was diluted in 6N methanolic ammonia and the solvents were evaporated under vacuum. The residue was purified by chromatography on silica gel (eluant: 3% to 5% methanol in DCM) to give the title compound as a beige foam (215 mg, 60%); NMR Spectrum (CDCl3) 1.73 (d, 3H), 3.06 (s, 3H), 3.14 (s, 3H), 5.43 (q, 1H), 5.80 (s, 2H), 6.81 (d, 1H), 6.93 (s, 1H), 7.48 (m, 2H), 7.60 (t, 1H), 7.84 (dd, 1H), 8.08 (s, 1H), 8.43 (s, 1H), 8.62 (s, 1H), 8.78 (s, 1H); Mass spectrum 474.

後処理

  1. customthe solvents were evaporated under vacuum
  2. additionAcetonitrile (5 ml) was added
  3. stirringThe mixture was stirred at 75° C. for 2 hours
  4. temperatureAfter cooling
  5. customthe solvents were evaporated under vacuum
  6. additionThe residue was diluted in 6N methanolic ammonia
  7. customthe solvents were evaporated under vacuum
  8. customThe residue was purified by chromatography on silica gel (eluant: 3% to 5% methanol in DCM)

出典と根拠

ORDレコード
ord-ef02f22c132a48a4884e9544a5cec33b
出典データセット
uspto-grants-2010_10
特許番号
US07820683B2

反応ノート

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