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Methyl 2-bromothiazole-5-carboxylate → 2-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-thiazole-5-carboxylic acid methyl ester

HRID 1366154
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HRID 1366154 반응식
C(OC(=O)[N:7]([C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][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.[CH3:43][O:44][C:45]([C:47]1[S:51][C:50](Br)=[N:49][CH:48]=1)=[O:46]>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>[CH3:43][O:44][C:45]([C:47]1[S:51][C:50]([C:11]2[N:10]3[CH:27]=[CH:28][N:29]=[C:9]3[C:8]([NH:7][C:30]3[CH:31]=[CH:32][C:33]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[CH:34][CH:35]=3)=[N:13][CH:12]=2)=[N:49][CH:48]=1)=[O:46]
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참가 물질

5

반응물 2

HCID 2773502Methyl 2-bromothiazole-5-carboxylateHCID 59023110(4-Morpholin-4-yl-phenyl)-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester

생성물 1

HCID 590230072-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-thiazole-5-carboxylic acid methyl ester수율 57.3%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물
촉매
HCID 6228Dimethylformamide용매

실험 절차

In the same way as described for Compound 212, step 3, using (4-morpholin-4-yl-phenyl)-(5-tributylstannanyl-imidazo[1,2-a]pyrazin-8-yl)-carbamic acid tert-butyl ester (0.25 g, 0.36 mmol), 2-bromo-thiazole-5-carboxylic acid methyl ester (0.159 g, 0.716 mmol), and Pd(PPh3)4 (0.041 g, 0.036 mmol) in DMF (4 mL). The reaction mixture is concentrated, treated with a mixture of (1:1) TFA-DCM and stirred at room temperature for 18 hours. The mixture is diluted with EtOAc and washed with a solution of sat. NaHCO3. The organic layers are dried over MgSO4, filtered and concentrated. Purification by silica gel column chromatography using 75:25 petroleum ether-EtOAc affords the title compound (90 mg, 57%). HPLC (254 nm): Rt 3.89 min (73%)

후처리

  1. concentrationThe reaction mixture is concentrated
  2. additiontreated with a mixture of (1:1) TFA-DCM
  3. additionThe mixture is diluted with EtOAc
  4. washwashed with a solution of sat. NaHCO3
  5. dry with materialThe organic layers are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel column chromatography

출처 및 근거

ORD 기록
ord-50da3f92923a4316bd2f798bac5a2af4
출처 데이터셋
uspto-grants-2011_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07893058B2

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