Picolyl chloride hydrochloride → 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine

HRID 1162200노트

반응식

HRID 1162200 반응식
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([NH:12][C:13]1[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=1)[NH:18][N:17]=[CH:16]3)=[N:5][CH:6]=[N:7]2.Cl.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29]Cl.[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([NH:12][C:13]1[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=1)[N:18]([CH2:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=1)[N:17]=[CH:16]3)=[N:5][CH:6]=[N:7]2

참가 물질

5

반응물 3

HCID 23392Picolyl chloride hydrochlorideHCID 24758Sodium hydrideHCID 686187815-fluoro-N-1H-indazol-5-ylquinazolin-4-amine

생성물 1

HCID 686183205-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine수율 41%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To a stirred partial solution of 5-fluoro-N-1H-indazol-5-ylquinazolin-4-amine (3.35 g, 12 mmol) and 2-picolyl chloride hydrochloride (2.07 g, 12.6 mmol) in DMF (60 ml) was added portion-wise, sodium hydride (60% dispersion in mineral oil, 1.01 g, 25.2 mmol). The reaction was maintained at ambient temperature by slight cooling and stirred for 18 hours. The reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution (5 ml) and evaporated under high vacuum. The residue was partitioned between 2.5M aqueous NaOH and DCM and the organic phase was dried over anhydrous Na2SO4 and evaporated. The product was purified by chromatography (5% methanol/ethyl acetate) and the crystallized by trituration with ether to give 5-fluoro-N-[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]quinazolin-4-amine (1.8 g, 41%); NMR spectrum (300 MHz) 5.75 (s, 2H), 6.97 (d, 1H), 7.27 (m, 1H), 7.41 (dd, 1H), 7.54-7.75 (m, 4H), 7.84 (q, 1H), 8.12 (d, 2H), 8.50 (m, 2H), 9.23 (d, 1H); Mass spectrum MH+ 371.

후처리

  1. temperatureby slight cooling
  2. customThe reaction mixture was quenched by addition of saturated aqueous ammonium chloride solution (5 ml)
  3. customevaporated under high vacuum
  4. customThe residue was partitioned between 2.5M aqueous NaOH and DCM
  5. dry with materialthe organic phase was dried over anhydrous Na2SO4
  6. customevaporated
  7. customThe product was purified by chromatography (5% methanol/ethyl acetate)
  8. customthe crystallized by trituration with ether

출처 및 근거

ORD 기록
ord-700fc3344a7a4f2085636a2ab559d85b
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820683B2

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