Diisopropylethylamine → HCID 178422437, 화합물

HRID 216426

반응식

HRID 216426 반응식
[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

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 21114231Cyclopropyl methyl hydroxylamine hydrochlorideHCID 178422438HCID 178422438, 화합물

생성물 1

HCID 178422437HCID 178422437, 화합물수율 45%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-121ce7e82f98487ba954785eaa75088e
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193229B2

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