Phosphate → HCID 86666694, compound

HRID 2045894Notes

Reaction equation

HRID 2045894 reaction equation
P([O-])([O-])([O-])=O.[Na].[Cl:7][C:8]1[CH:9]=[C:10]([C:19]2[N:20]=[C:21]([NH:24][C:25](=[O:41])[CH2:26][C:27]3[C:35]4[C:34](=[O:36])[N:33]([CH3:37])[C:32](=[O:38])[N:31]([CH3:39])[C:30]=4[O:29][C:28]=3[CH3:40])[S:22][CH:23]=2)[CH:11]=[CH:12][C:13]=1[O:14][C:15]([F:18])([F:17])[F:16].[P:42]([O:54][CH2:55]Cl)([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43].[I-].[Na+]>CC(C)=O>[P:42]([O:54][CH2:55][N:20]1[C:19]([C:10]2[CH:11]=[CH:12][C:13]([O:14][C:15]([F:18])([F:16])[F:17])=[C:8]([Cl:7])[CH:9]=2)=[CH:23][S:22][C:21]1=[N:24][C:25](=[O:41])[CH2:26][C:27]1[C:35]2[C:34](=[O:36])[N:33]([CH3:37])[C:32](=[O:38])[N:31]([CH3:39])[C:30]=2[O:29][C:28]=1[CH3:40])([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:43]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 5238Sodium IodideHCID 5360545SodiumHCID 11701630Di-tert-butyl (chloromethyl) phosphate2×HCID 46918165HCID 46918165, compound

Product 1

HCID 86666694HCID 86666694, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

The title compound was prepared according to the general procedure as described in method C for the preparation of phosphate derivatives by the reaction of sodium salt of N-{4-[3-chloro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl}-2-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydrofuro[2,3-d]pyrimidin-5-yl)acetamide (50 g, 0.09 mol) with di-tert-butyl chloromethyl phosphate (Intermediate 1) (58.6 g, 0.23 mol) in presence of sodium iodide (10.8 g, 0.072 mol) in dry acetone (1250 ml) to obtain 50g of a product as a pale yellow solid. Alternatively the title compound was also prepared according to the general procedure as described in step 2 of method B for the preparation of phosphate derivatives by coupling N-{4-[3-chloro-4-(trifluoromethoxy)phenyl]-1,3-thiazol-2-yl}-2-(1,3,6-trimethyl-2,4-dioxo-1,2,3,4-tetrahydrofuro[2,3-d]pyrimidin-5-yl)acetamide (500 mg, 0.945 mmol) with freshly prepared di-tert-butyl iodomethyl phosphate (Intermediate 2) (1.16 g, 3.307 mmol) using sodium hydride (57 mg, 1.418 mmol) in dry DMF (5 ml) to yield 197 mg of product as an off-white solid; 1H NMR (300 MHz, CDCl3): δ 1.49 (br s, 18H), 2.36 (s, 3H), 3.32 (s, 3H), 3.53 (s, 3H), 4.18 (s, 2H), 6.43 (d, J=6.3 Hz, 2H), 7.22-7.29 (m, 1H), 7.34 (d, J=8.4 Hz, 1H), 7.78 (t, J=8.7 Hz, 1H), 8.05 (s, 1H); ESI (m/z): 751 (M+H)+.

Sources & evidence

ORD record
ord-7b02964c90b04ab497c81788b5ee4dda
Source dataset
uspto-grants-2013_11
Patent number
US08592398B2

Reaction notes

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