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

HRID 1162215

反応式

HRID 1162215 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-08c4343fa54545e79cfde7fd3b4bf047
出典データセット
uspto-grants-2010_10
特許番号
US07820683B2

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