5-Bromothiophene-3-carboxamide → HCID 59022988、化合物

HRID 1924919ノート

反応式

HRID 1924919 の反応式
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

参加物

6

反応物 2

HCID 189380635-Bromothiophene-3-carboxamideHCID 67117498HCID 67117498、化合物

生成物 2

HCID 222AmmoniaHCID 59022988HCID 59022988、化合物収率 40%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
85 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-75be7d350ef942979c67b65cde781e9a
出典データセット
uspto-grants-2012_05
特許番号
US08178530B2

反応ノート

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