Dimethylformamide → HCID 86674324, compound

HRID 1028097Notes

Reaction equation

HRID 1028097 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([N:23]([C:31]2[N:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][N:32]=2)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:7]=[C:8]([C:10]2[S:14][C:13]([N:15]3[CH2:21][CH2:20][CH2:19][NH:18][C:17](=[O:22])[CH2:16]3)=[N:12][CH:11]=2)[CH:9]=1)([O-])=O.[Cl-].[NH4+].CN(C=O)C.C(OCC)(=O)C.CCCCCC>C(O)C.[Fe]>[NH2:1][C:4]1[CH:5]=[C:6]([N:23]([C:31]2[N:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=[CH:33][N:32]=2)[C:24](=[O:30])[O:25][C:26]([CH3:28])([CH3:29])[CH3:27])[CH:7]=[C:8]([C:10]2[S:14][C:13]([N:15]3[CH2:21][CH2:20][CH2:19][NH:18][C:17](=[O:22])[CH2:16]3)=[N:12][CH:11]=2)[CH:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium Chloride2×HCID 21226206Ethyl acetate hexaneHCID 71075112HCID 71075112, compound

Product 1

HCID 86674324HCID 86674324, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

To a suspension of tert-butyl {3-nitro-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]phenyl}[4-(trifluoromethyl)pyrimidin-2-yl]carbamate (314 mg, 0.542 mmol) in ethanol (9 mL) at room temperature under nitrogen, was added iron (605 mg, 10.84 mmol) and a saturated aqueous solution of ammonium chloride (0.25 mL). The mixture was stirred at 40° C. for 30 minutes. N,N′-dimethylformamide (5 mL) was added and the mixture was stirred at 40° C. for 3 hours. An additional portion of iron (300 mg, 5.4 mmol) and saturated aqueous solution of ammonium chloride (1.1 mL) were then added and the resulting mixture was stirred at 40° C. for 2 hours. The reaction was then cooled to room temperature, and concentrated under reduced pressure to remove volatiles. The resulting suspension was filtered through celite, rinsing successively with N,N′-dimethylformamide, ethyl acetate, dichloromethane, and 2-methyltetrahydrofuran. The filtrate was concentrated to remove the volatiles, then diluted with ethyl acetate, washed with water (5×), brine (1×), dried over sodium sulfate, and concentrated to provide a beige solid. This solid was swished in 1:1 ethyl acetate/hexane, the solids collected by filtration, rinsed successively with 1:1 ethyl acetate/hexane and hexane, and dried to afford 250 mg (0.46 mmol, 85%) of tert-butyl {3-amino-5-[2-(3-oxo-1,4-diazepan-1-yl)-1,3-thiazol-5-yl]phenyl}[4-(trifluoromethyl)pyrimidin-2-yl]carbamate as a beige solid.

Workup

  1. stirringthe mixture was stirred at 40° C. for 3 hours
  2. stirringthe resulting mixture was stirred at 40° C. for 2 hours
  3. temperatureThe reaction was then cooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customto remove volatiles
  6. filtrationThe resulting suspension was filtered through celite
  7. washrinsing successively with N,N′-dimethylformamide, ethyl acetate, dichloromethane, and 2-methyltetrahydrofuran
  8. concentrationThe filtrate was concentrated
  9. customto remove the volatiles
  10. additiondiluted with ethyl acetate
  11. washwashed with water (5×), brine (1×)
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated
  14. customto provide a beige solid
  15. filtrationthe solids collected by filtration
  16. washrinsed successively with 1:1 ethyl acetate/hexane and hexane
  17. customdried

Sources & evidence

ORD record
ord-12d095e83200422f950cad62c729a631
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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