Phosphate → [4-[2,3-Difluoro-4-(trifluoromethyl)phenyl]-2-{[(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl dihydrogen phosphate

HRID 1521885Notes

Reaction equation

HRID 1521885 reaction equation
[P:1]([O-:6])([O-:5])([O:3][CH3:4])=[O:2].P([O-])([O-])([O-])=O.[Na].[F:13][C:14]1[C:19]([F:20])=[C:18]([C:21]([F:24])([F:23])[F:22])[CH:17]=[CH:16][C:15]=1[C:25]1[N:26]=[C:27]([NH:30][C:31](=[O:46])[CH2:32][C:33]2[C:41]3[C:40](=[O:42])[N:39]([CH3:43])[C:38](=[O:44])[N:37]([CH3:45])[C:36]=3[S:35][N:34]=2)[S:28][CH:29]=1.P(OCI)(OC(C)(C)C)(OC(C)(C)C)=O>CN(C=O)C>[P:1]([OH:6])([OH:5])([O:3][CH2:4][N:26]1[C:25]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([F:23])([F:24])[F:22])=[C:19]([F:20])[C:14]=2[F:13])=[CH:29][S:28][C:27]1=[N:30][C:31](=[O:46])[CH2:32][C:33]1[C:41]2[C:40](=[O:42])[N:39]([CH3:43])[C:38](=[O:44])[N:37]([CH3:45])[C:36]=2[S:35][N:34]=1)=[O:2]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 5360545SodiumHCID 12691389Methyl PhosphateHCID 46928084N-{4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}-2-(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamideHCID 58196853Di-Tert-Butyl Iodomethyl Phosphate2×

Product 1

HCID 57377336[4-[2,3-Difluoro-4-(trifluoromethyl)phenyl]-2-{[(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl dihydrogen phosphate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Di-tert-butyl 4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-2-{[(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetyl]imino}-1,3-thiazol-3(2H)-yl]methyl phosphate: The title compound was prepared according to the general procedure as described in step 2 of method B for the preparation of phosphate derivatives by the reaction of sodium salt of N-{4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}-2-(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide (2.0 g, 3.71 mmol) with freshly prepared di-tert-butyl iodomethyl phosphate (Intermediate 2) (1.948 g, 5.56 mol) in dry DMF (20 ml) to yield 1.035 g of product as a white solid. Alternatively the title compound was also prepared according to the general procedure as described in method A for the preparation of phosphate derivatives by coupling N-{4-[2,3-difluoro-4-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl}-2-(5,7-dimethyl-4,6-dioxo-4,5,6,7-tetrahydro[1,2]thiazolo[5,4-d]pyrimidin-3-yl)acetamide (500 mg, 0.967 mmol) with freshly prepared di-tert-butyl iodomethyl phosphate (Intermediate 2) (1.18 g, 3.38 mmol) in presence of sodium hydride (60% dispersion in mineral oil, 58 mg, 1.45 mmol) in dry DMF (5 ml) to yield 135 mg of product as an off-white solid. 1H NMR (300 MHz, CDCl3): δ 1.46 (s, 18H), 3.36 (s, 3H), 3.57 (s, 3H), 4.66 (s, 2H), 6.38 (s, 2H), 7.40 (t, J=7.8 Hz, 1H), 7.64 (s, 1H), 8.15 (t, J=7.5 Hz, 1H); ESI-MS (m/z) 739.06 (M−H)−.

Sources & evidence

ORD record
ord-eb51cf55f6f64d53bbdce7efb40b4b2e
Source dataset
uspto-grants-2015_07
Patent number
US09073955B2

Reaction notes

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