Methyl chloroformate → HCID 66801353, compound

HRID 2366274Notes

Reaction equation

HRID 2366274 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].CCN(C(C)C)C(C)C.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[C:17]=1[C:23]1[S:24][C:25]2[C:26]([NH2:33])=[N:27][CH:28]=[C:29]([F:32])[C:30]=2[N:31]=1>C1COCC1>[CH3:5][O:4][C:2](=[O:3])[NH:33][C:26]1[C:25]2[S:24][C:23]([C:17]3[C:18]([Cl:22])=[CH:19][CH:20]=[CH:21][C:16]=3[Cl:15])=[N:31][C:30]=2[C:29]([F:32])=[CH:28][N:27]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 66801891HCID 66801891, compound

Product 1

HCID 66801353HCID 66801353, compoundYield 20.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl chloroformate (18 mg, 0.191 mmol) and DIPEA (42 μL, 0.24 mmol) in THF (1.0 mL) was added 2-(2,6-dichlorophenyl)-7-fluorothiazolo[5,4-c]pyridin-4-ylamine (50 mg, 0.159 mmol). The reaction mixture was stirred at room temperature for 2.5 hours, then heated at 50° C. for 2 hours and left standing at room temperature for 18 hours. The crude reaction mixture was partitioned between EtOAc and brine. The aqueous phase was extracted with EtOAc and the combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-50% EtOAc in pentane to afford the title compound as a white solid (12 mg, 20%). 1H NMR (400 MHz, DMSO-d6): δ 10.87 (s, 1H), 8.48 (d, J=1.8 Hz, 1H), 7.77-7.65 (m, 3H), 3.73 (s, 3H). LCMS (Method C): RT=4.74 min, m/z: 372 [M+H+].

Workup

  1. temperatureheated at 50° C. for 2 hours
  2. waitleft
  3. waitstanding at room temperature for 18 hours
  4. customThe crude reaction mixture
  5. customwas partitioned between EtOAc and brine
  6. extractionThe aqueous phase was extracted with EtOAc
  7. dry with materialthe combined organic layers were dried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-50% EtOAc in pentane

Sources & evidence

ORD record
ord-a0a62d384f07406fb8ad4c9723e7b078
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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