Formic Acid → HCID 59160681, compound

HRID 1500053Notes

Reaction equation

HRID 1500053 reaction equation
C(OC(=O)C)(=O)C.[CH:8]([OH:10])=O.[CH2:11]([O:18][C:19]1[N:24]=[C:23]([NH2:25])[C:22]([F:26])=[CH:21][N:20]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:11]([O:18][C:19]1[N:24]=[C:23]([NH:25][CH:8]=[O:10])[C:22]([F:26])=[CH:21][N:20]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 57818833HCID 57818833, compound

Product 1

HCID 59160681HCID 59160681, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A 10 mL Schlenk-type flask was charged with acetic anhydride (4.0 mL, 42 mmol), formic acid (2.0 mL, 53 mmol), and CH2Cl2 (20 mL), and was cooled to 0° C. under nitrogen. N,N-Dimethylpyridin-4-amine (275 mg, 2.25 mmol) was added, and the resulting solution was allowed to stir at room temperature for 10 min. Solid 2-(benzyloxy)-5-fluoropyrimidin-4-amine (495 mg, 2.26 mmol) was added, and the reaction stirred for another 21 h at room temperature. The crude reaction mixture was diluted with CH2Cl2 (50 mL) and washed with water (50 mL), saturated aqueous NaHCO3 (50 mL), and water (50 mL). The organic solution was dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was then purified by flash column chromatography (EtOAc/hexane gradient) to afford the title compound (295.8 mg, 53%) as a white solid: mp 153-157° C.; 1H NMR (300 MHz, DMSO-d6) δ 11.29 (bs, 1H), 9.34 (s, 1H), 8.48 (d, J=2.6 Hz, 1H), 7.29-7.46 (m, 5H), 5.32 (s, 2H); MS (ESI) m/z 248 (M+H)+, 246 (M−H)−.

Workup

  1. stirringthe reaction stirred for another 21 h at room temperature
  2. customThe crude reaction mixture
  3. washwashed with water (50 mL), saturated aqueous NaHCO3 (50 mL), and water (50 mL)
  4. dry with materialThe organic solution was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was then purified by flash column chromatography (EtOAc/hexane gradient)

Sources & evidence

ORD record
ord-17aca7c1392f44909daf7b2c2b5806c0
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

Loading…