Acetonitrile → (3R,5S)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol

HRID 1443010ノート

反応式

HRID 1443010 の反応式
[Si]([O:8][C@H:9]1[CH2:13][N:12](C(OC(C)(C)C)=O)[C@H:11]([CH2:21][O:22][C:23]2[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]3[C:24]=2[C:25]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([F:42])=[C:38]([Cl:43])[CH:37]=2)=[N:26][CH:27]=[N:28]3)[CH2:10]1)(C(C)(C)C)(C)C.C(#N)C>FC(F)(F)C(O)=O>[Cl:43][C:38]1[CH:37]=[C:36]([CH:41]=[CH:40][C:39]=1[F:42])[NH:35][C:25]1[C:24]2[C:29](=[CH:30][C:31]([O:33][CH3:34])=[CH:32][C:23]=2[O:22][CH2:21][C@H:11]2[NH:12][CH2:13][C@H:9]([OH:8])[CH2:10]2)[N:28]=[CH:27][N:26]=1

参加物

4

反応物 2

HCID 6342AcetonitrileHCID 86607807tert-Butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy)-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate

生成物 1

HCID 68675709(3R,5S)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidin-3-ol収率 69.3%

試薬・触媒・溶媒 1

HCID 6422Trifluoroacetic acid溶媒

実験手順

tert-Butyl (2S,4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[({4-[3-chloro-4-fluoroanilino]-7-methoxyquinazolin-5-yl}oxy)methyl]pyrrolidine-1-carboxylate (860 mg) was dissolved in trifluoroacetic acid (40 ml) and stirred at room temperature for 24 hours. The reaction mixture was then concentrated in vacuo, and excess water was added, followed by the careful addition of saturated aqueous sodium hydrogen carbonate. The mixture was extracted with 3% methanol in DCM and the organic layer was separated, dried (Na2SO4) and concentrated in vacuo to leave a light brown foam. Trituration with cold acetonitrile gave (3R,5S)-5-[({4-[3-chloro-4-fluoroanilino]-7-methoxy-quinazolin-5-yl}oxy)methyl]-pyrrolidin-3-ol as an off-white solid (394 mg, 69%); NMR spectrum (DMSO-d6) 10.50-10.00 (br, 1H), 8.49 (s, 1H), 8.25 (dd, 1H), 7.90-7.84 (m, 1H), 7.44 (t, 1H), 6.82 (d, 1H), 6.76 (d, 1H), 4.92 (br s, 1H), 4.38 (dd, 1H), 4.32 (br s, 1H), 3.92-3.86 (m, 4H), 3.77-3.23 (br s, 1H), 3.09 (dd, 1H), 2.83 (d, 1H), 1.88 (dd, 1H), 1.74-1.65 (m, 1H); Mass spectrum MH+ 419.

後処理

  1. concentrationThe reaction mixture was then concentrated in vacuo, and excess water
  2. additionwas added
  3. additionfollowed by the careful addition of saturated aqueous sodium hydrogen carbonate
  4. extractionThe mixture was extracted with 3% methanol in DCM
  5. customthe organic layer was separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto leave a light brown foam

出典と根拠

ORDレコード
ord-6ee9e76c297d433eb6b3f70aaffd0134
出典データセット
uspto-grants-2010_02
特許番号
US07659279B2

反応ノート

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