Tetrahydrofuran → HCID 57829836, compound

HRID 1855470Notes

Reaction equation

HRID 1855470 reaction equation
C(O[C:4]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]3)=[C:15]([O:25][CH3:26])[CH:14]=2)[N:7]=1)=[O:5])C.[CH:27]1([Mg]Br)[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:42][CH2:41][CH2:40]C1>>[CH:27]1([C:4]([CH:40]2[CH2:41][CH2:42]2)([C:6]2[CH:11]=[CH:10][N:9]=[C:8]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]4)=[C:15]([O:25][CH3:26])[CH:14]=3)[N:7]=2)[OH:5])[CH2:29][CH2:28]1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10340Sodium CarbonateHCID 57829859HCID 57829859, compoundHCID 178418630HCID 178418630, compound

Product 1

HCID 57829836HCID 57829836, compoundYield 88%

Conditions

Temperature
0 °C

Procedure

To a solution of 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-pyrimidine-4-carboxylic acid ethyl ester (46 mg, 0.13 mmol) in tetrahydrofurane (2.5 mL) was added at 0° C. over 1 min a 0.5 M solution of cyclopropylmagnesiumbromide in tetrahydrofurane (1.02 mL, 0.51 mmol). The reaction mixture was stirred at 0° C. for 15 min followed by 1.5 h at 20° C. The mixture was poured on saturated sodium carbonate solution (5 mL) and the mixture was extracted with ethyl acetate (40 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate and evaporated under reduced pressure. The residual material was purified by chromatography on silica gel using dichloromethane/0-10% methanol as eluent to give the title compound as light yellow foam (44 mg, 88%). MS ISP (m/e): 392.3 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.45 (d, 1H), 7.64 (s, 1H), 7.56 (d, 1H), 7.23 (s, 1H), 7.19 (d, 1H), 7.08 (dd, 1H), 7.00 (d, 1H), 6.88 (s, 1H), 4.15 (s, 1H), 3.87 (s, 3H), 2.30 (s, 3H), 1.14 (m, 2H), 0.70, 0.50, 0.35, 0.25 (4 m, 4×2H).

Workup

  1. waitfollowed by 1.5 h at 20° C
  2. extractionthe mixture was extracted with ethyl acetate (40 mL)
  3. washThe organic layer was washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residual material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-a84fec66a71144188bc10078d18f5e38
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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