Tetrahydrofuran → HCID 44192420, compound

HRID 1855469Notes

Reaction equation

HRID 1855469 reaction equation
C([O:3][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)C.[CH2:27]([Mg]Br)[CH3:28].C(=O)([O-])[O-].[Na+].[Na+].O1CC[CH2:39][CH2:38]1>>[CH3:26][O:25][C:15]1[CH:14]=[C:13]([NH:12][C:8]2[N:7]=[C:6]([C:4]([OH:3])([CH2:27][CH3:28])[CH2:38][CH3:39])[CH:11]=[CH:10][N:9]=2)[CH:18]=[CH:17][C:16]=1[N:19]1[CH:23]=[C:22]([CH3:24])[N:21]=[CH:20]1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 10340Sodium CarbonateHCID 57829859HCID 57829859, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 44192420HCID 44192420, compoundYield 9%

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 1 M solution of ethylmagnesiumbromide in tetrahydrofurane (0.43 mL, 0.43 mmol). The reaction mixture was stirred at 0° C. for 15 min followed by 1 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 (4 mg, 9%) as yellow oil. MS ISP (m/e): 368.2 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.42 (d, 1H), 7.66 (d, 1H), 7.65 (s, 1H), 7.39 (s, 1H), 7.20 (d, 1H), 7.06 (dd, 1H), 6.89 (s, 1H), 6.79 (d, 1H), 4.32 (br s, 1H), 3.88 (s, 3H), 2.31 (s, 3H), 2.35 (m, 4H), 0.76 (t, 6H).

Workup

  1. waitfollowed by 1 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-a3baa16788c4430cb036335f6b4cf180
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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