Acetylethanolamine → 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol

HRID 1162201

反応式

HRID 1162201 の反応式
[H-].[Na+].[OH:3]CCNC(=O)C.F[C:11]1[CH:20]=[CH:19][CH:18]=[C:17]2[C:12]=1[C:13]([NH:21][C:22]1[CH:23]=[C:24]3[C:28](=[CH:29][CH:30]=1)[N:27]([CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=1)[N:26]=[CH:25]3)=[N:14][CH:15]=[N:16]2>CC(N(C)C)=O>[N:33]1[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=1[CH2:31][N:27]1[C:28]2[C:24](=[CH:23][C:22]([NH:21][C:13]3[C:12]4[C:11]([OH:3])=[CH:20][CH:19]=[CH:18][C:17]=4[N:16]=[CH:15][N:14]=3)=[CH:30][CH:29]=2)[CH:25]=[N:26]1

参加物

5

反応物 3

HCID 8880AcetylethanolamineHCID 24758Sodium hydrideHCID 686183205-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine

生成物 1

HCID 1363467194-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol収率 36%

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
120 °C

実験手順

To a stirred suspension of sodium hydride (60% in mineral oil, 1.68 g, 42 mmol) in DMA (25 ml) was slowly added N-(2-hydroxyethyl)acetamide (1.80 g, 17.5 mmol). When the effervescence had subsided, 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine (2.60 g, 7.0 mmol) was added and the mixture was heated at 120° C. for 18 hours. The reaction was quenched by addition of saturated aqueous NH4Cl (5 ml) and evaporated (high vacuum). The residue was stirred with water (100 ml) giving a gelatinous precipitate, which was filtered off and washed with water. The product was purified by chromatography (silica, dry loaded, 5 to 10% methanol/DCM) and crystallized by trituration with ether to give 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol (928 mg, 32%); NMR spectrum (373 K) 5.72 (s, 2H), 6.77 (m, 3H), 7.03 (d, 1H), 7.23 (dd, 1H), 7.44 (t, 1H), 7.50 (d, 1H), 7.59 (d, 1H), 7.70 (t, 1H), 8.07 (s, 1H), 8.13 (s, 1H), 8.27 (s, 1H), 8.52 (d, 1H), 11.87 (br s, 1H); Mass spectrum MH+ 369.

後処理

  1. customThe reaction was quenched by addition of saturated aqueous NH4Cl (5 ml)
  2. customevaporated (high vacuum)
  3. customgiving a gelatinous precipitate, which
  4. filtrationwas filtered off
  5. washwashed with water
  6. customThe product was purified by chromatography (silica, dry loaded, 5 to 10% methanol/DCM)
  7. customcrystallized by trituration with ether

出典と根拠

ORDレコード
ord-7f6db8f661d44af8ae4cb6a15b05dacd
出典データセット
uspto-grants-2010_10
特許番号
US07820683B2

関連ノート

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