Lithium Hexamethyldisilazide → HCID 66779815, compound

HRID 1958029Notes

Reaction equation

HRID 1958029 reaction equation
[CH:1]1([C:4]2[NH:9][C:8]3[N:10]=[C:11]([N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[S:12][C:7]=3[C:6](=[O:19])[N:5]=2)[CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[C:33]=1[CH3:42]>O1CCCC1>[CH:1]1([C:4]2[N:9]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[C:33]=3[CH3:42])[C:8]3[N:10]=[C:11]([N:13]4[CH2:14][CH2:15][O:16][CH2:17][CH2:18]4)[S:12][C:7]=3[C:6](=[O:19])[N:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27756171-(Bromomethyl)-2-methyl-3-(trifluoromethyl)benzeneHCID 178517406HCID 178517406, compound

Product 1

HCID 66779815HCID 66779815, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-cyclopropyl-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (50 mg, 0.180 mmol) in Tetrahydrofuran (THF) (1000 μl) was stirred at 0° C. for 15 min, then lithium bis(trimethylsilyl)amide (359 μl, 0.359 mmol) in THF was added and stirring was continued for 30 min. 1-(bromomethyl)-2-methyl-3-(trifluoromethyl)benzene (54.6 mg, 0.216 mmol) in Tetrahydrofuran (THF) (300 μl) was added and the mixture was stirred at 65° C. overnight. The reaction mixture was concentrated and the residue purified by reversed-phase HPLC to provide the major regio-isomer, 5-cyclopropyl-4-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (Example 70). (9 mg, 11%); LC/MS: MS (ES+) m/e 451 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.83-0.92 (m, 2H), 0.98-1.07 (m, 2H), 1.86-1.97 (m, 1H), 2.51 (s, 3H), 3.45-3.56 (m, 4H), 3.63-3.73 (m, 4H), 5.76 (s, 2H), 6.92 (d, J=7.83 Hz, 1H), 7.37 (m, 1H), 7.64 (d, J=7.8 Hz, 1H).

Workup

  1. stirringthe mixture was stirred at 65° C. overnight
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-126f760869704934a53e16406de8b4df
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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