5-Bromothiophene-3-carboxamide → HCID 59022988, 화합물

HRID 1924919노트

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HRID 1924919 반응식
C(OC(=O)[N:7]([C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)=[CH:32][CH:31]=1)[C:8]1[C:9]2[N:10]([CH:27]=[CH:28][N:29]=2)[C:11]([Sn](CCCC)(CCCC)CCCC)=[CH:12][N:13]=1)(C)(C)C.Br[C:45]1[S:49][CH:48]=[C:47]([C:50]([NH2:52])=[O:51])[CH:46]=1>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH3:7].[CH3:42][N:39]1[CH2:40][CH2:41][N:36]([C:33]2[CH:34]=[CH:35][C:30]([NH:7][C:8]3[C:9]4[N:10]([CH:27]=[CH:28][N:29]=4)[C:11]([C:45]4[S:49][CH:48]=[C:47]([C:50]([NH2:52])=[O:51])[CH:46]=4)=[CH:12][N:13]=3)=[CH:31][CH:32]=2)[CH2:37][CH2:38]1

참가 물질

6

반응물 2

HCID 189380635-Bromothiophene-3-carboxamideHCID 67117498HCID 67117498, 화합물

생성물 2

HCID 222AmmoniaHCID 59022988HCID 59022988, 화합물수율 40%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
85 °C

실험 절차

To a solution of [4-(4-methyl-piperazin-1-yl)-phenyl]-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester (0.106 g, 0.15 mmol) in DMF (3 mL) is added 5-bromo-thiophene-3-carboxylic acid amide (0.062 g, 0.3 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.015 mmol). The solution is degassed and heated at 85° C. for 18 hours. The reaction mixture is diluted with ethyl acetate and washed with water (3×) and brine. The aqueous layers are backwashed with ethyl acetate and the organic layers are combined, dried (MgSO4), and concentrated. The crude mixture is then stirred in (1:1) TFA: dichloromethane (3 mL) for 2 hours at room temperature. The resulting solution is diluted with ethyl acetate and washed with water, sat. NaHCO3 and brine. The aqueous layers are backwashed with ethyl acetate and the organic layers are combined, dried (MgSO4), and concentrated. The crude material is purified by flash column chromatography using 99:1 and 95:5 DCM:NH3 (7M in MeOH), to give 5-{8-[4-(4-methyl-piperazin-1-yl)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-thiophene-3-carboxylic acid amide (0.013 g, 20%) as a yellow solid. LCMS: Rt 2.79 min, (93.3%), m/z (APCI) 434 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.26 (3H, s), 2.48-2.53 (4H, m), 3.14 (4H, m), 6.96 (2H, d), 7.42 (1H, br s), 7.61 (1H, s), 7.78 (1H, s), 7.82 (2H, d), 7.92 (1H, s), 7.99 (1H, br s), 8.21 (1H, s), 8.31 (1H, s), 9.61 (1H, s).

후처리

  1. customThe solution is degassed
  2. additionThe reaction mixture is diluted with ethyl acetate
  3. washwashed with water (3×) and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. additionThe resulting solution is diluted with ethyl acetate
  7. washwashed with water, sat. NaHCO3 and brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude material is purified by flash column chromatography

출처 및 근거

ORD 기록
ord-75be7d350ef942979c67b65cde781e9a
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08178530B2

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