Formic Acid → Hydroxy{(1S)-4-pyrimidin-2-yl-1-[({4-[5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]piperazin-1-yl}sulfonyl)methyl]butyl}formamide

HRID 1723801Notes

Reaction equation

HRID 1723801 reaction equation
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[OH:11][NH:12][CH:13]([CH2:36][CH2:37][CH2:38][C:39]1[N:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH2:14][S:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[CH:28][C:27]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[CH:26][N:25]=2)[CH2:20][CH2:19]1)(=[O:17])=[O:16]>C1COCC1>[OH:11][N:12]([C@H:13]([CH2:14][S:15]([N:18]1[CH2:23][CH2:22][N:21]([C:24]2[N:29]=[CH:28][C:27]([O:30][CH2:31][C:32]([F:33])([F:34])[F:35])=[CH:26][N:25]=2)[CH2:20][CH2:19]1)(=[O:17])=[O:16])[CH2:36][CH2:37][CH2:38][C:39]1[N:44]=[CH:43][CH:42]=[CH:41][N:40]=1)[CH:1]=[O:2]

Participants

5

Reactant 3

HCID 284Formic Acid2×HCID 7918Acetic AnhydrideHCID 866145742-(4-{[2-(Hydroxyamino)-5-pyrimidin-2-ylpentyl]sulfonyl}piperazin-1-yl)-5-(2,2,2-trifluoroethoxy)pyrimidine

Product 1

HCID 57559244Hydroxy{(1S)-4-pyrimidin-2-yl-1-[({4-[5-(2,2,2-trifluoroethoxy)pyrimidin-2-yl]piperazin-1-yl}sulfonyl)methyl]butyl}formamideYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To formic acid (114 mL, 3.03 mol) at 0° C. was added acetic anhydride (28.6 mL, 0.303 mol) and the mixture was stirred at RT for 10 minutes. The reaction was then recooled to 0° C., and added to a solution of 2-(4-{[2-(hydroxyamino)-5-pyrimidin-2-ylpentyl]sulfonyl}piperazin-1-yl)-5-(2,2,2-trifluoroethoxy)pyrimidine (30.6 g, 60.5 mmol) and formic acid (114 mL, 3.03 mol) in THF (600 mL). The reaction was brought to room temperature and stirred for one hour. Volatiles were then removed in vacuo, and the residue azeotroped with toluene (2×300 mL). The residue was then dissolved in methanol (300 mL) and heated to 40° C. for one hour. The solution was then cooled to room temperature and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 10% MeOH in EtOAc) to give the racemic compound as a pale orange foam (22.94 g, 43 mmol, 71%).

Workup

  1. customwas then recooled to 0° C.
  2. customwas brought to room temperature
  3. stirringstirred for one hour
  4. customVolatiles were then removed in vacuo
  5. customthe residue azeotroped with toluene (2×300 mL)
  6. dissolutionThe residue was then dissolved in methanol (300 mL)
  7. temperatureheated to 40° C. for one hour
  8. temperatureThe solution was then cooled to room temperature
  9. concentrationconcentrated in vacuo
  10. customThe residue was then purified by flash chromatography (silica gel, 10% MeOH in EtOAc)

Sources & evidence

ORD record
ord-6226cf4261ba4b2c85f86287d9f68575
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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