Formic Acid → HCID 57833459, compound

HRID 729977Notes

Reaction equation

HRID 729977 reaction equation
Cl[S:2]([N:5]=C=O)(=[O:4])=[O:3].C(O)=O.S(Cl)(=O)(=O)N.[NH2:16][C:17]1[N:22]=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[CH:20]=[C:19]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][C:38]3[CH:43]=[CH:42][N:41]=[C:40]([C:44]([F:47])([F:46])[F:45])[CH:39]=3)=[CH:33][CH:32]=2)[N:18]=1>CN(C)C(=O)C.CO>[S:2](=[O:3])(=[O:4])([O:29][C:26]1[CH:27]=[CH:28][C:23]([C:21]2[CH:20]=[C:19]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([O:37][C:38]4[CH:43]=[CH:42][N:41]=[C:40]([C:44]([F:46])([F:47])[F:45])[CH:39]=4)=[CH:33][CH:32]=3)[N:18]=[C:17]([NH2:16])[N:22]=2)=[CH:24][CH:25]=1)[NH2:5]

Participants

7

Reactant 4

HCID 284Formic AcidHCID 24499Chlorosulfamic acidHCID 70918Chlorosulfonyl isocyanateHCID 136183339HCID 136183339, compound

Product 1

HCID 57833459HCID 57833459, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Procedure

To neat chlorosulfonyl isocyanate (0.166 g, 1.37 mmol) was added dropwise formic acid (97%, 0.63 g, 1.37 mmol) while cooling in ice-water bath. The mixture was stirred at rt until gas evolution ceased. The resulting sulfamoyl chloride was added to a solution of 4-{2-amino-6-[(4-{[2-(trifluoromethyl)pyridin-4-yl]oxy}phenyl) amino] pyrimidin-4-yl} phenol (0.06 g, 0.14 mmol, Example 51) in dry N,N-dimethylacetamide at 0° C. The reaction mixture was then stirred at rt for 12 h. The solution was diluted with methanol and separated by preparative HPLC. The desired fractions were combined, basified with saturated sodium carbonate, and extracted with EtOAc (3×). The extracts were combined, washed with brine, dried over magnesium sulfate, and evaporated to give desired product, 0.025 g (35%). 1H NMR (DMSO-d6) δ 9.42 (s, 1H), 8.59 (d, 1H), 8.09 (d, 2H), 7.98 (m, 2H), 7.85 (m, 2H), 7.35 (m, 3H), 7.10 (m, 3H), 6.42 (s, 1H), 6.36 (s, 2H); MS ES 519 (M+H)+calcd 519.

Workup

  1. stirringThe reaction mixture was then stirred at rt for 12 h
  2. customseparated by preparative HPLC
  3. extractionextracted with EtOAc (3×)
  4. washwashed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-0b9892ade7ff49dd9db46018f8d29076
Source dataset
uspto-grants-2009_09
Patent number
US07582646B2

Reaction notes

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