4-Cyclopropyl-1,3-thiazol-2-amine → 6-{(E)-2-[2-(Cyclobutylmethoxy)-3-(difluoromethoxy)phenyl]vinyl}-N-(4-cyclopropyl-1,3-thiazol-2-yl)imidazo[2,1-b][1,3]thiazole-5-carboxamide

HRID 1882171Notes

Reaction equation

HRID 1882171 reaction equation
[CH:1]1([CH2:5][O:6][C:7]2[C:12]([O:13][CH:14]([F:16])[F:15])=[CH:11][CH:10]=[CH:9][C:8]=2/[CH:17]=[CH:18]/[C:19]2[N:20]=[C:21]3[N:25]([C:26]=2[C:27](O)=[O:28])[CH:24]=[CH:23][S:22]3)[CH2:4][CH2:3][CH2:2]1.[CH:30]1([C:33]2[N:34]=[C:35]([NH2:38])[S:36][CH:37]=2)[CH2:32][CH2:31]1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C1COCC1.CN(C=O)C>[CH:1]1([CH2:5][O:6][C:7]2[C:12]([O:13][CH:14]([F:16])[F:15])=[CH:11][CH:10]=[CH:9][C:8]=2/[CH:17]=[CH:18]/[C:19]2[N:20]=[C:21]3[N:25]([C:26]=2[C:27]([NH:38][C:35]2[S:36][CH:37]=[C:33]([CH:30]4[CH2:32][CH2:31]4)[N:34]=2)=[O:28])[CH:24]=[CH:23][S:22]3)[CH2:2][CH2:3][CH2:4]1

Participants

7

Reactant 3

HCID 6744564-Cyclopropyl-1,3-thiazol-2-amineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593699316-{(E)-2-[2-(Cyclobutylmethoxy)-3-(difluoromethoxy)phenyl]vinyl}imidazo[2,1-b][1,3]thiazole-5-carboxylic acid

Product 1

HCID 468341396-{(E)-2-[2-(Cyclobutylmethoxy)-3-(difluoromethoxy)phenyl]vinyl}-N-(4-cyclopropyl-1,3-thiazol-2-yl)imidazo[2,1-b][1,3]thiazole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

The title compound was prepared according to the general procedure (Method B) by coupling Intermediate 10 (200 mg, 0.476 mmol) with 4-cyclopropyl-1,3-thiazol-2-amine (73 mg, 0.523 mmol) in the presence of EDCI hydrochloride (182 mg, 0.952 mmol) and DMAP (53 mg, 0.476 mmol) in a mixture of THF and DMF (1:1, 4 mL) to give 120 mg of the product as an off-white solid; 1H NMR (300 MHz, CDCl3) δ 0.80-0.86 (m, 2H), 0.88-0.96 (m, 2H), 1.23-1.29 (m, 1H), 1.85-1.94 (m, 4H), 2.00-2.10 (m, 2H), 2.72-2.80 (m, 1H), 3.98 (d, J=6.6 Hz, 2H), 6.36 (s, 1H), 6.58 (t, J=75.3 Hz, 1H), 6.95 (d, J=4.5 Hz, 1H), 7.00-7.10 (m, 2H), 7.48-7.53 (m, 1H), 7.62 (d, J=15.6 Hz, 1H), 7.82 (d, J=15.6 Hz, 1H), 8.24-8.30 (m, 1H); APCI-MS (m/z) 543.31 (MH)+.

Sources & evidence

ORD record
ord-534d7ab552834a1cac4bf3326748db73
Source dataset
uspto-grants-2012_11
Patent number
US08318928B2

Reaction notes

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