Lithium Hexamethyldisilazide → HCID 66780392, compound

HRID 1958014Notes

Reaction equation

HRID 1958014 reaction equation
[CH3:1][C:2]1[NH:7][C:6]2[N:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[S:10][C:5]=2[C:4](=[O:17])[N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:28][C:29]1[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31]Br>O1CCCC1>[Cl:28][C:29]1[C:36]([Cl:37])=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][N:7]1[C:6]2[N:8]=[C:9]([N:11]3[CH2:12][CH2:13][O:14][CH2:15][CH2:16]3)[S:10][C:5]=2[C:4](=[O:17])[N:3]=[C:2]1[CH3:1]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27346021-(Bromomethyl)-2,3-dichlorobenzeneHCID 178433428HCID 178433428, compound

Product 1

HCID 66780392HCID 66780392, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-methyl-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (75 mg, 0.297 mmol) in Tetrahydrofuran (THF) (1.5 mL) was stirred at 0° C. for 15 min, then lithium bis(trimethylsilyl)amide (446 μl, 0.446 mmol, 1.0 M in THF) was added and stirring was continued for 30 min. 2,3-Dichlorobenzyl bromide (86 mg, 0.357 mmol) was added and the mixture was allowed to warm to room temperature and stirred overnight. Additional stirring at 65° C. for 2 h completed the reaction resulting in a mixture of the desired product and the regio-isomer. The reaction was concentrated and the residue was purified by reversed-phase HPLC to provide the product, 4-[(2,3-dichlorophenyl)methyl]-5-methyl-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one (28 mg, 23%). LC/MS: MS (ES+) m/e 411 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H) 3.52 (m, 4H) 3.64-3.72 (m, 4H) 5.60 (s, 2H) 6.90 (d, J=7.3 Hz, 1H) 7.33 (m, 1H) 7.64 (d, J=8.0 Hz, 1H).

Workup

  1. stirringstirred overnight
  2. stirringAdditional stirring at 65° C. for 2 h

Sources & evidence

ORD record
ord-0b7b4cd93ed941de87b8e6958cbb8fad
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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