Triethylamine → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 216441

반응식

HRID 216441 반응식
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19](O)=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:22])[CH:3]=1.C1C=[CH:25][C:26]2N(O)N=N[C:27]=2[CH:28]=1.C(N(CC)CC)C.Cl.C1([N:44](C)[OH:45])CC1.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(=O)C.O>[CH:26]1([CH2:25][O:45][NH:44][C:19]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[Cl:22])=[C:17]([F:18])[C:13]3[N:14]=[CH:15][NH:16][C:12]=3[CH:11]=2)=[O:20])[CH2:27][CH2:28]1

참가 물질

9

반응물 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 211141586-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acidHCID 21114231Cyclopropyl methyl hydroxylamine hydrochloride

생성물 1

HCID 98251576-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide수율 89%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10b (22 mg, 0.057 mmol) is dissolved in DMF (1 mL) and HOBt (9 mg, 0.062 mmol) followed by triethyl amine (18 μL, 0.132 mmol) is added. Cyclopropyl methyl hydroxylamine hydrochloride (8 mg, 0.062 mmol) is added followed by EDCI (14 mg, 0.074 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and water and the layers separated. The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine. The organic layer is dried (MgSO4) and concentrated under reduced pressure to give 23 mg (89%) pure desired product. MS APCI (+) m/z 455, 453 (M+ Br pattern) detected; MS APCI (−) m/z 453, 451 (M− Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.69 (broad s, 1H), 8.43 (s, 1H), 7.62 (d, 1H), 7.28 (dd, 1H), 6.42 (m, 1H), 3.63 (d, 2H), 1.03 (m, 1H), 0.48 (m, 2H), 0.19 (m, 2H); 19F NMR (376 MHz, DMSO-d6) −132.95 (s).

후처리

  1. additionis added
  2. customthe layers separated
  3. washThe organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine
  4. dry with materialThe organic layer is dried (MgSO4)
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-e7a94e0649504cff8d340c9448a90973
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08193229B2

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