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

HRID 1162201

반응식

HRID 1162201 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
120 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7f6db8f661d44af8ae4cb6a15b05dacd
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820683B2

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