Diisopropylethylamine → HCID 178422437、化合物

HRID 31967

反応式

HRID 31967 の反応式
[F:1][C:2]1[C:7]2[NH:8][CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([C:11]([OH:13])=O)[C:3]=1[NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=1[CH3:22].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=[CH:53][CH:54]=[CH:55][C:50]2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl.C1([N:69](C)[OH:70])CC1>C1COCC1.C(Cl)Cl>[CH:54]1([CH2:53][O:70][NH:69][C:11]([C:4]2[C:3]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=3[CH3:22])=[C:2]([F:1])[C:7]3[NH:8][CH:9]=[N:10][C:6]=3[CH:5]=2)=[O:13])[CH2:55][CH2:50]1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 21114231Cyclopropyl methyl hydroxylamine hydrochlorideHCID 178422438HCID 178422438、化合物

生成物 1

HCID 178422437HCID 178422437、化合物収率 45%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

7-Fluoro-6-(4-bromo-2-methyl-phenylamino)-1H-benzoimidazole-5-carboxylic acid 10a (48 mg, 0.132 mmol) is dissolved in 1:1 THF: methylene chloride (1 mL) and Hunig's base (0.23 μL, 1.32 mmol) is added followed by PyBOP (82 mg, 0.158 mmol). After a few minutes, cyclopropyl methyl hydroxylamine hydrochloride (20 mg, 0.158 mmol) (WO 00/42022) is added. After the reaction is complete, the mixture is partitioned between methylene chloride and saturated NaHCO3 solution. The layers are separated and the organic layer is washed with saturated NaHCO3 and brine. The organic layer is dried (Na2SO4) and concentrated under reduced pressure. After purification by FCC (elute with 20:1 methlene chloride/MeOH), 25 mg (45%) of pure desired product is isolated: MS ESI (+) m/z 435, 433 (M+1 Br pattern) detected; MS ESI (−) m/z 433, 431 (M−1 Br pattern) detected; 1H NMR (400 MHz, CDCl3) δ 8.15 (s, 1H), 8.02 (s, 1H), 7.28 (s, 1H), 7.43 (d, 1H), 7.07 (dd, 1H), 6.36 (m, 1H), 3.70 (d, 2H), 2.38 (s, 3H), 0.86 (m, 1H), 0.41 (m, 2H), 0.13 (m, 2H); 19F NMR (376 MHz, CDCl3)-134.05 (s).

後処理

  1. waitAfter a few minutes
  2. customthe mixture is partitioned between methylene chloride and saturated NaHCO3 solution
  3. customThe layers are separated
  4. washthe organic layer is washed with saturated NaHCO3 and brine
  5. dry with materialThe organic layer is dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customAfter purification
  8. washby FCC (elute with 20:1 methlene chloride/MeOH)

出典と根拠

ORDレコード
ord-b8a11fdb83e64933a854839501e7fed3
出典データセット
uspto-grants-2008_09
特許番号
US07425637B2

関連ノート

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