2-Methoxy-4-(tributylstannyl)thiazole → 1-[5-[2-(Ethylcarbamoylamino)-7-(2-methoxythiazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acid

HRID 712257Notes

Reaction equation

HRID 712257 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][C:20]([N:23]3[CH2:28][CH2:27][C:26]([CH3:34])([C:29]([O:31]CC)=[O:30])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)[CH:3]=1.[CH3:35][O:36][C:37]1[S:38][CH:39]=[C:40]([Sn](CCCC)(CCCC)CCCC)[N:41]=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>[CH2:15]([NH:14][C:12]([NH:11][C:8]1[S:9][C:10]2[C:2]([C:40]3[N:41]=[C:37]([O:36][CH3:35])[S:38][CH:39]=3)=[CH:3][C:4]([C:17]3[CH:22]=[N:21][C:20]([N:23]4[CH2:24][CH2:25][C:26]([CH3:34])([C:29]([OH:31])=[O:30])[CH2:27][CH2:28]4)=[N:19][CH:18]=3)=[CH:5][C:6]=2[N:7]=1)=[O:13])[CH3:16]

Participants

5

Reactant 2

HCID 27632642-Methoxy-4-(tributylstannyl)thiazoleHCID 86663956Ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate

Product 1

HCID 569534901-[5-[2-(Ethylcarbamoylamino)-7-(2-methoxythiazol-4-yl)-1,3-benzothiazol-5-yl]pyrimidin-2-yl]-4-methyl-piperidine-4-carboxylic acidYield 65.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A stirred mixture of ethyl 1-(5-(7-bromo-2-(3-ethylureido)benzo[d]thiazol-5-yl)pyrimidin-2-yl)-4-methylpiperidine-4-carboxylate (150 mg, 0.274 mmol), tetrakis(triphenylphosphine)palladium (16 mg, 0.0138 mmol) and 2-methoxy-4-(tributylstannyl)thiazole (0.33 mL, 0.822 mmol) in anhydrous DMF (3.0 mL) was purged with N2 for 20 min. The reaction vessel was sealed and heated at 110° C. for 10 h. After cooling to rt, the mixture was diluted with water (50 mL) and extracted with EtOAc (3×20 mL) which was washed with brine (30 mL) and dried (MgSO4). The solvent was removed in vacuo and the residue purified by flash silica chromatography eluting with 0 to 100% EtOAc in iso-hexane to give 99 mg of the desired product as an off white gummy solid.

Workup

  1. customwas purged with N2 for 20 min
  2. customThe reaction vessel was sealed
  3. temperatureAfter cooling to rt
  4. additionthe mixture was diluted with water (50 mL)
  5. extractionextracted with EtOAc (3×20 mL) which
  6. washwas washed with brine (30 mL)
  7. dry with materialdried (MgSO4)
  8. customThe solvent was removed in vacuo
  9. customthe residue purified by flash silica chromatography
  10. washeluting with 0 to 100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-b5078aa6c806412f9887f4d74c8c2767
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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