Ethyl 2-aminothiazole-4-carboxylate → HCID 67454055, compound

HRID 1853131Notes

Reaction equation

Br[CH2:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([NH:11][C:12]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)([CH3:14])[CH3:13])=[N:9][CH:10]=1)=O.[CH2:22]([O:24][C:25]([C:27]1[N:28]=[C:29]([NH2:32])[S:30][CH:31]=1)=[O:26])[CH3:23]>CC(CC)=O>[Cl:21][C:20]1[C:15]([C:12]([NH:11][C:8]2[N:7]=[CH:6][C:5]([C:3]3[N:32]=[C:29]4[N:28]([CH:2]=3)[C:27]([C:25]([O:24][CH2:22][CH3:23])=[O:26])=[CH:31][S:30]4)=[CH:10][N:9]=2)([CH3:14])[CH3:13])=[N:16][CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a 20 dram vial was added 2-bromo-1-(2-(2-(3-chloropyridin-2-yl)propan-2-ylamino)pyrimidin-5-yl)ethanone (103 mg, 0.28 mmol), ethyl-2-aminothiazole-4-carboxylate (48 mg, 0.28 mmol), and methylethylketone (2 mL). The mixture was heated to 90° C. in a sealed tube and stirred overnight. The reaction was then concentrated and purified by silica gel chromatography (EtOAc/hex) to afford 33 mg of ethyl 6-(2-(2-(3-chloropyridin-2-yl)propan-2-ylamino)pyrimidin-5-yl)imidazo[2,1-b]thiazole-3-carboxylate as a tan solid. This compound was dissolved in methanol (1 mL) and ammonium hydroxide (3 mL) was added. The resulting mixture was heated in a microwave reactor to 135° C. and stirred for 15 min. The reaction was concentrated, followed by the addition of HBTU (68 mg, 179 μmol), HOBt (24 mg, 179 μmol), NH4Cl (48 mg, 1.1 mmol), DIPEA (78 μL, 441 μmol), and NMP (2 mL). The reaction was stirred for 2 h and then purified directly by reverse phase chromatography to afford 18 mg of 6-(2-(2-(3-chloropyridin-2-yl)propan-2-ylamino)pyrimidin-5-yl)imidazo[2,1-b]thiazole-3-carboxamide as an off-white solid (M+H=414.1).

Workup

concentrationThe reaction was then concentrated
custompurified by silica gel chromatography (EtOAc/hex)

Sources & evidence

ORD record: ord-d4bc58a557dc479b8709fa1b9e3eba8b
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962632B2

Reaction notes

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