Phosphate → Di-tert-butyl [2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-3(2H)-yl]methyl phosphate

HRID 2045888Notes

Reaction equation

HRID 2045888 reaction equation
P([O-])([O-])([O-])=O.[CH3:6][N:7]1[C:12]2[S:13][CH:14]=[C:15]([CH2:16][C:17]([NH:19][C:20]3[S:21][CH:22]=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[C:27]([F:35])[CH:26]=4)[N:24]=3)=[O:18])[C:11]=2[C:10](=[O:36])[N:9]([CH3:37])[C:8]1=[O:38].[P:39]([O:51][CH2:52]I)([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40].[H-].[Na+]>CN(C=O)C>[P:39]([O:51][CH2:52][N:24]1[C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:32])([F:34])[F:33])=[C:27]([F:35])[CH:26]=2)=[CH:22][S:21][C:20]1=[N:19][C:17](=[O:18])[CH2:16][C:15]1[C:11]2[C:10](=[O:36])[N:9]([CH3:37])[C:8](=[O:38])[N:7]([CH3:6])[C:12]=2[S:13][CH:14]=1)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])([O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:40]

Participants

6

Reactant 4

HCID 1061PhosphateHCID 24758Sodium hydrideHCID 469278382-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)-N-{4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}acetamideHCID 58196853Di-Tert-Butyl Iodomethyl Phosphate2×

Product 1

HCID 86666690Di-tert-butyl [2-{[(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)acetyl]imino}-4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-3(2H)-yl]methyl phosphate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The title compound was prepared according to the general procedure as described in method A for the preparation of phosphate derivatives by coupling reaction of 2-(1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-5-yl)-N-{4-[3-fluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}acetamide (500 mg, 1.004 mmol) with freshly prepared di-tert-butyl iodomethyl phosphate (Intermediate 2) (1.22 g, 3.514 mmol) in the presence of sodium hydride (60% dispersion in mineral oil, 60.24 mg, 1.506 mmol) in dry DMF (5 ml) to yield 150 mg of pure product as an off-white solid. 1H NMR (300 MHz, CDCl3): δ 1.49 (s, 18H), 3.34 (s, 3H), 3.57 (s, 3H), 4.43 (s, 2H), 6.36-6.44 (m, 2H), 6.79 (s, 1H), 7.33 (s, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.71-7.81 (m, 2H); ESI (m/z): 721 (M+H)+.

Sources & evidence

ORD record
ord-e9c83f5e1128462d9ca7cdda621020cb
Source dataset
uspto-grants-2013_11
Patent number
US08592398B2

Reaction notes

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