Potassium Carbonate → Ethyl 6-{(E)-2-[2-(cyclobutylmethoxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylate

HRID 1882142Notes

Reaction equation

HRID 1882142 reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[C:5]([OH:25])=[C:6](/[CH:10]=[CH:11]/[C:12]2[N:13]=[C:14]3[N:18]([C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][S:15]3)[CH:7]=[CH:8][CH:9]=1.Br[CH2:28][CH:29]1[CH2:32][CH2:31][CH2:30]1.C(=O)([O-])[O-].[K+].[K+].FC(F)OC1C(OCC(C)(C)C)=C(/C=C/C2N=C3N(C=2C(O)=O)C=CS3)C=CC=1>CN(C)C=O>[CH:29]1([CH2:28][O:25][C:5]2[C:4]([O:3][CH:2]([F:1])[F:26])=[CH:9][CH:8]=[CH:7][C:6]=2/[CH:10]=[CH:11]/[C:12]2[N:13]=[C:14]3[N:18]([C:19]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:17]=[CH:16][S:15]3)[CH2:32][CH2:31][CH2:30]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 2734658(Bromomethyl)cyclobutaneHCID 59369921Ethyl 6-{(E)-2-[3-(difluoromethoxy)-2-hydroxyphenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylateHCID 684073456-{(E)-2-[3-(Difluoromethoxy)-2-(2,2-dimethylpropoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylic acid

Product 1

HCID 67549158Ethyl 6-{(E)-2-[2-(cyclobutylmethoxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylateYield 88.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Alkylation of Intermediate 6 (500 mg, 1.315 mmol) with (bromomethyl)cyclobutane (178 mg, 1.578 mmol) in presence of potassium carbonate (199 mg, 1.446 mmol) in anhydrous N,N-dimethylformamide (5 mL) as described in Intermediate 7A gave 520 mg of the product as a white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.40 (t, J=6.9 Hz, 3H), 1.84-1.93 (m, 4H), 2.02-2.10 (m, 2H), 2.70-2.76 (m, 1H), 3.93 (d, J=6.9 Hz, 2H), 4.41 (q, J=6.9 Hz, 2H), 7.19 (t, J=74.7 Hz, 1H), 7.20-7.28 (m, 2H), 7.42-7.51 (m, 1H), 7.54-7.60 (m, 1H), 7.70-7.78 (m, 1H), 7.85 (d, J=15.9 Hz, 1H), 8.13 (d, J=4.2 Hz, 1H); APCI-MS (m/z) 449.18 (M+H)+.

Sources & evidence

ORD record
ord-c190ead2a04b4774a9cb624dc1004009
Source dataset
uspto-grants-2012_11
Patent number
US08318928B2

Reaction notes

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