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 1921778Notes

Reaction equation

HRID 1921778 reaction equation
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]

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

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%)

Workup

  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

Sources & evidence

ORD record
ord-655b87ab1e7f4315be313408e231977c
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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