Potassium Carbonate → Ethyl 4-{[4-(6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3,4-dihydro-2h-1,4-benzoxazin-6-yl]amino}-1-methyl-1h-imidazole-2-carboxylate

HRID 885994Notes

Reaction equation

HRID 885994 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][CH2:8][N:7]([C:11]3[S:12][C:13]4[CH2:14]C(C)(C)N[C:17](=O)[C:18]=4[N:19]=3)[C:6]=2[CH:23]=1.C(=O)([O-])[O-:25].[K+].[K+].[NH:30]1CC[CH2:35][C@H:31]1[C:32](O)=O.Cl.[CH2:39]([O:41][C:42]([C:44]1[N:45]([CH3:50])[CH:46]=[C:47]([NH2:49])[N:48]=1)=[O:43])[CH3:40]>CS(C)=O.[Cu]I>[CH3:32][C:31]1([CH3:35])[NH:30][C:14](=[O:25])[C:13]2[S:12][C:11]([N:7]3[C:6]4[CH:23]=[C:2]([NH:49][C:47]5[N:48]=[C:44]([C:42]([O:41][CH2:39][CH3:40])=[O:43])[N:45]([CH3:50])[CH:46]=5)[CH:3]=[CH:4][C:5]=4[O:10][CH2:9][CH2:8]3)=[N:19][C:18]=2[CH2:17]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 22349687ethyl 4-amino-1-methyl-1H-imidazole-2-carboxylate hydrochlorideHCID 685972362-(6-Bromo-2,3-dihydrobenzo[1,4]oxazin-4-yl)-6,6-dimethyl-6,7-dihydro-[1,3]thiazolo[5,4-d]pyridin-4(5h)-one

Product 1

HCID 67186781Ethyl 4-{[4-(6,6-dimethyl-4-oxo-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)-3,4-dihydro-2h-1,4-benzoxazin-6-yl]amino}-1-methyl-1h-imidazole-2-carboxylateYield 3.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of Example 39 (0.4 g, 1.015 mmol), copper(I) iodide (0.038 g, 0.203 mmol), potassium carbonate (0.420 g, 3.04 mmol), proline (0.045 g, 0.406 mmol) and 4-amino-1-methylimidazole-2-carboxylic acid ethyl ester hydrochloride (0.417 g, 2.03 mmol) in DMSO (3 mL) was heated to 120° C. for 16 h in a sealed tube. It was concentrated in vacuo and purified by preparative HPLC (Method 6) to give the title compound (0.007 g, 1.6%) as a yellow solid. δH (DMSO-d6) 8.39 (1H, s), 7.99 (1H, d, J 2.1 Hz), 7.52 (1H, s), 7.06 (1H, s), 6.83-6.76 (2H, m), 4.32-4.18 (4H, m), 4.10-4.01 (2H, m), 3.92 (3H, s), 2.83 (2H, s), 1.32-1.22 (9H, m). LCMS (ES+) 483/484 (M+H)+, RT 2.94 minutes (Method 1).

Workup

  1. concentrationIt was concentrated in vacuo
  2. custompurified by preparative HPLC (Method 6)

Sources & evidence

ORD record
ord-ba9a5e751c5e4cb3b019b5cb2884df22
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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