Cesium carbonate → ditert-butyl [(2Z)-2-[4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyanophenyl]sulfonylimino-1,3-thiazol-3-yl]methyl phosphate

HRID 46276Notes

Reaction equation

HRID 46276 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C:17]3[S:18][CH:19]=[CH:20][N:21]=3)(=[O:15])=[O:14])=[CH:9][C:8]=2[C:22]#[N:23])=[C:4]([C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)[CH:3]=1.[P:32]([O:44][CH2:45]Cl)([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[P:32]([O:44][CH2:45][N:21]1[CH:20]=[CH:19][S:18]/[C:17]/1=[N:16]\[S:13]([C:10]1[CH:11]=[CH:12][C:7]([O:6][C:5]2[CH:24]=[CH:25][C:2]([Cl:1])=[CH:3][C:4]=2[C:26]2[N:30]([CH3:31])[N:29]=[CH:28][CH:27]=2)=[C:8]([C:22]#[N:23])[CH:9]=1)(=[O:14])=[O:15])([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:33]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 594365994-[4-Chloro-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzenesulfonamide

Product 1

HCID 59436487ditert-butyl [(2Z)-2-[4-[4-chloro-2-(2-methylpyrazol-3-yl)phenoxy]-3-cyanophenyl]sulfonylimino-1,3-thiazol-3-yl]methyl phosphateYield 84.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-[4-Chloro-2-(1-methyl-1H-pyrazol-5-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzenesulfonamide, (Example 170, 200 mg, 0.000424 mol), di-tert-butyl chloromethyl phosphate (J. Med. Chem. 51 (2008) p 1111-1114, supplimentary data) (160 mg, 0.000619 mol) and cesium carbonate (420 mg, 0.00129 mol) were stirred in dimethylformamide (2 mL) at 60° C. for 18 hours. The mixture was cooled then partitioned between tert-butylmethyl ether (80 mL) and water (40 mL), the organic layer was dried over anhydrous sodium sulphate, filtered and the solvent removed in vacuo to give the title compound as a pale yellow gum, (250 mg).

Workup

  1. temperatureThe mixture was cooled
  2. customthen partitioned between tert-butylmethyl ether (80 mL) and water (40 mL)
  3. dry with materialthe organic layer was dried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-eb9168d4d0454f33aaae5d15c6791e6a
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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