Triphenylphosphine → methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate

HRID 1162215노트

반응식

HRID 1162215 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:26]([OH:28])=[CH:25][CH:24]=[CH:23][C:22]=4[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1.[C:29]([O:34][CH3:35])(=[O:33])[C@H:30]([CH3:32])O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH:17][C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[O:28][C@H:30]([CH3:32])[C:29]([O:34][CH3:35])=[O:33])[N:21]=[CH:20][N:19]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1

참가 물질

5

반응물 3

HCID 11776TriphenylphosphineHCID 94386methyl (S)-lactateHCID 1363467194-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol

생성물 1

HCID 86627834methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate수율 80.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

DTAD (11.48 g, 49.9 mmol) was added portion-wise to an ice-cooled solution of 4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-ol (7.36 g, 20 mmol), (S)-methyl lactate (2.29 ml, 24 mmol) and triphenylphosphine (13.1 g, 49.9 mmol) in DCM (200 ml). The mixture was stirred at room temperature for 1 hour. The mixture was extracted with 2N hydrochloric acid (2×50 ml). The hydrochloric layers were combined and washed with DCM. The pH of the solution was adjusted to pH 9 by slow addition of concentrated aqueous ammonia while cooling. This aqueous solution was extracted with DCM (2×100 ml). These DCM layers were combined, washed with water and brine and dried over MgSO4. After evaporation of the solvents, the residue was purified by chromatography on silica gel (eluant: 4% methanol in DCM) to give methyl (2R)-2-[(4-{[1-(pyridin-2-ylmethyl)-1H-indazol-5-yl]amino}quinazolin-5-yl)oxy]propanoate as a yellowish solid (7.35 g, 80%); NMR Spectrum (CDCl3) 1.80 (d, 3H), 3.85 (s, 3H), 5.15 (q, 1H), 5.76 (s, 2H), 6.79 (d, 1H), 6.85 (d, 1H), 7.18 (m, 1H), 7.43 (d, 1H), 7.50 (d, 1H), 7.63-7.54 (m, 2H), 7.70 (dd, 1H), 8.11 (s, 1H), 8.38 (s, 1H), 8.59 (br d, 1H), 8.63 (s, 1H); Mass spectrum MH+ 455.

후처리

  1. extractionThe mixture was extracted with 2N hydrochloric acid (2×50 ml)
  2. washwashed with DCM
  3. additionThe pH of the solution was adjusted to pH 9 by slow addition of concentrated aqueous ammonia
  4. temperaturewhile cooling
  5. extractionThis aqueous solution was extracted with DCM (2×100 ml)
  6. washwashed with water and brine
  7. dry with materialdried over MgSO4
  8. customAfter evaporation of the solvents
  9. customthe residue was purified by chromatography on silica gel (eluant: 4% methanol in DCM)

출처 및 근거

ORD 기록
ord-08c4343fa54545e79cfde7fd3b4bf047
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07820683B2

반응 노트

불러오는 중…