4-Aminopyrimidine → 4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide

HRID 1473686노트

반응식

HRID 1473686 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:20])=[O:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)[C:5]([O:33][CH3:34])=[CH:4][C:3]=1[C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1.[N:42]1[CH:47]=[CH:46][C:45]([NH2:48])=[N:44][CH:43]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[C:17]3[C:12](=[CH:13][C:14]([S:18]([NH:48][C:45]4[CH:46]=[CH:47][N:42]=[CH:43][N:44]=4)(=[O:19])=[O:20])=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)[C:5]([O:33][CH3:34])=[CH:4][C:3]=1[C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=1

참가 물질

5

반응물 3

HCID 689584-AminopyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 86687767Perfluorophenyl 4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinazoline-7-sulfonate

생성물 1

HCID 866877694-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide수율 86%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

A flask was charged with perfluorophenyl 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinazoline-7-sulfonate (Intermediate ZZZZZ; 0.060 g, 0.098 mmol), pyrimidin-4-amine (9.81 mg, 0.103 mmol), and THF (0.982 ml) and cooled to 0° C. LHMDS (1.0M in THF) (0.206 ml, 0.206 mmol) was added drop wise and the reaction was stirred for 30 minutes. The reaction was quenched with saturated ammonium chloride solution, diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-10% MeOH:DCM) to afford 4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)-N-(pyrimidin-4-yl)quinazoline-7-sulfonamide (0.044 g, 0.084 mmol, 86% yield) as an -off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=9.49 (s, 1H), 8.57 (s, 1H), 8.51 (d, J=1.6 Hz, 1H), 8.22 (d, J=6.9 Hz, 1H), 8.08 (dd, J=1.8, 8.8 Hz, 1H), 7.91 (d, J=8.9 Hz, 1H), 7.67 (s, 1H), 7.59 (dt, J=6.3, 8.1 Hz, 1H), 7.48-7.41 (m, 2H), 7.37-7.29 (m, 2H), 7.00 (d, J=5.0 Hz, 1H), 3.74 (s, 3H). m/z (ESI) 522.0 (M+H)+.

후처리

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. additiondiluted with ethyl acetate
  3. washwashed with water
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. dry with materialthe combined organic layers were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-10% MeOH:DCM)

출처 및 근거

ORD 기록
ord-04f25befd26444ad8a20c61b3d000240
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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