Allyl bromide → 3-allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

HRID 1867265ノート

反応式

HRID 1867265 の反応式
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH:8]3[CH:11]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:12]([C:14]([N:16]([O:18][CH3:19])[CH3:17])=[O:15])=[N:13][N:7]3[C:6]=2[CH:26]=1.F[C:28]1[CH:29]=CC2OC[C@@H]3[C@H](C4C=CC=CC=4)C(C(N(OC)C)=O)=NN3C=2[CH:52]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C(Br)C=C>C1COCC1.C1(C)C=CC=CC=1>[CH2:29]([C:11]1([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:8]2[CH2:9][O:10][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:26][C:6]=3[N:7]2[N:13]=[C:12]1[C:14]([N:16]([O:18][CH3:19])[CH3:17])=[O:15])[CH:28]=[CH2:52]

参加物

7

反応物 4

HCID 7841Allyl bromideHCID 2733832Lithium HexamethyldisilazideHCID 730455398-Fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]-benzoxazine-2-carboxamideHCID 86624795trans-8-Fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

生成物 1

HCID 866247943-allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

Either cis (1-7) or trans-8-Fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-5, 4.8 g, 13.5 mmol) was dissolved in anhydrous THF (50 mL) and cooled to −78° C. in an acetone/dry ice bath under an N2 atmosphere. The resulting solution was treated with LHMDS (16.2 mL of a 1M toluene solution, 16.2 mmol) and stirred 2 minutes to produce a deep red color. Allyl bromide (2.3 mL, 26.9 mmol) was added neat and the solution was allowed to stir 10 minutes at −78° C. and then removed from the ice bath. Upon reaching ambient temperature, the reaction was judged complete by TLC and quenched by at addition of sat. aqueous NH4Cl (100 mL). The mixture was extracted with Et2O (3×100 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified using flash column chromatography (ISCO Redisep 120 g SiO2 column, 0-40% EtOAc/hexanes gradient) to provide pure 3-allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-6; a racemic mixture): 1H NMR (300 MHz, CDCl3) δ 7.40-7.22 (m, 3H), 7.20-7.12 (m, 3H), 6.77 (dd, J=8.9, 5.2 Hz, 1H), 6.53 (dt, J=8.6, 3.1 Hz, 1H), 5.57 (m, 1H), 5.27 (d, J=16.8 Hz, 1H), 5.22 (d, J=7.6 Hz, 1H), 4.12 (dd, J=10.5, 3.5 Hz, 1H), 3.90 (s, 3H), 3.63 (dd, J=11.0, 3.6 Hz, 1H), 3.37 (dd, J=13.7, 6.0 Hz, 1H), 3.32 (s, 3H), 2.96 (m, 2H); MS (M+H+, C22H22FN3O3) 396.3 found 396.4 required.

後処理

  1. customto produce a deep red color
  2. stirringto stir 10 minutes at −78° C.
  3. customremoved from the ice bath
  4. customUpon reaching ambient temperature
  5. customquenched by at addition of sat. aqueous NH4Cl (100 mL)
  6. extractionThe mixture was extracted with Et2O (3×100 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified

出典と根拠

ORDレコード
ord-e9563ada41b144bcb53efacf9273f2d8
出典データセット
uspto-grants-2009_12
特許番号
US07632833B2

反応ノート

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