Water → HCID 86760736, compound

HRID 2117758Notes

Reaction equation

HRID 2117758 reaction equation
[CH:1]([N:4]1[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([S:22](=[O:37])(=[O:36])[N:23]([CH2:32][CH2:33][O:34][CH3:35])[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[CH:18][CH:17]=3)[N:10]=2)=[CH:7][N:6]=[CH:5]1)([CH3:3])[CH3:2].C([Li])CCC.CN([CH:46]=[O:47])C.O>C1COCC1>[CH:46]([C:5]1[N:4]([CH:1]([CH3:3])[CH3:2])[C:8]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([S:22](=[O:36])(=[O:37])[N:23]([CH2:32][CH2:33][O:34][CH3:35])[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])=[CH:20][CH:21]=3)[N:10]=2)=[CH:7][N:6]=1)=[O:47]

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 69309147HCID 69309147, compoundHCID 178418339Butyllithium

Product 1

HCID 86760736HCID 86760736, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-(1-Isopropylimidazol-5-yl)-2-{4-[N-(2-methoxyethyl)-N-(2-trimethylsilylethoxymethyl)sulphamoyl]anilino}pyrimidine (Method 106; 1.22 g, 2.33 mmol), was dissolved in anhydrous THF (70 ml), under nitrogen. The solution was cooled to −78° C. and n-butyl lithium (3.48 ml of a 1.6 N solution in hexanes, 5.57 mmol), was added slowly, maintaining the temperature at less than −65° C. The reaction mixture was then stirred at −78° C. for 30 minutes, then DMF (345 μl, 4.46 mmol), was added and mixture allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was then poured into water (100 ml), and extracted with EtOAc (2×50 ml). The organic extracts were combined, washed with water (50 ml), brine (50 ml), and dried. The volatiles were removed and the residue was purified by chromatography on silica gel eluting with 3% MeOH in DCM, to give the title product, (307 mg, 24%), as a pale yellow foam. NMR: 0.02 (s, 9H), 0.83 (dd, 2H), 1.63 (d, 6H), 3.28 (s, 3H), 3.37 (t, 2H), 3.42 (dd, 2H), 3.52 (t, 2H), 4.78 (s, 2H), 5.71 (m, 1H), 7.40 (d, 1H), 7.82 (d, 2H), 7.92 (s, 1H), 8.01 (d, 2H), 8.78 (d, 1H), 9.91 (s, 1H); m/z: 573 [MH]−.

Workup

  1. temperaturemaintaining the temperature at less than −65° C
  2. temperatureto warm to ambient temperature
  3. stirringstirred for 1 hour
  4. extractionextracted with EtOAc (2×50 ml)
  5. washwashed with water (50 ml), brine (50 ml)
  6. customdried
  7. customThe volatiles were removed
  8. customthe residue was purified by chromatography on silica gel eluting with 3% MeOH in DCM

Sources & evidence

ORD record
ord-5fe7716a018345d59c42b7cbb781d291
Source dataset
uspto-grants-2008_10
Patent number
US07442697B2

Reaction notes

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