Lithium Hexamethyldisilazide → 4-(2,3-Dichlorobenzyl)-2-(2-methylmorpholino)thiazolo[4,5-d]pyrimidin-7(4H)-one

HRID 1958018Notes

Reaction equation

HRID 1958018 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:11][CH:12]1[CH2:17][N:16]([C:18]2[S:19][C:20]3[C:25](=[O:26])[N:24]=[CH:23][NH:22][C:21]=3[N:27]=2)[CH2:15][CH2:14][O:13]1.Br[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=1[Cl:37]>C1COCC1>[Cl:37][C:31]1[C:32]([Cl:36])=[CH:33][CH:34]=[CH:35][C:30]=1[CH2:29][N:22]1[C:21]2[N:27]=[C:18]([N:16]3[CH2:15][CH2:14][O:13][CH:12]([CH3:11])[CH2:17]3)[S:19][C:20]=2[C:25](=[O:26])[N:24]=[CH:23]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27346021-(Bromomethyl)-2,3-dichlorobenzeneHCID 178430095HCID 178430095, compound

Product 1

HCID 667798264-(2,3-Dichlorobenzyl)-2-(2-methylmorpholino)thiazolo[4,5-d]pyrimidin-7(4H)-oneYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

LiHMDS (0.9 N, 2.7 mL, 2.4 mmol) was added to a solution of 2-(2-methylmorpholino)thiazolo[4,5-d]pyrimidin-7(4H)-one (300 mg, 1.2 mmol) in THF (6.0 mL) at 0° C. The reaction mixture was stirred for an hour. 1-(bromomethyl)-2,3-dichlorobenzene (285 mg, 1.2 mmol) was added to the mixture and the resultant mixture was stirred for 18 hours. The reaction was quenched by water and extracted with dichloromethane. The organic layer was dried, concentrated and purified through silica gel chromatography to give the desired product as a solid (210 mg, 43%). 1H NMR (300 MHz, d6-DMSO) δ 8.48 (s, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.35 (m, 1H), 7.18 (d, J=7.8 Hz, 1H), 5.47 (s, 2H), 3.89 (m, 1H), 3.82˜3.75 (m, 2H), 3.56˜3.52 (m, 2H), 3.26˜3.16 (m, 1H), 2.91 (m, 1H), 1.14 (d, J=6.0 Hz, 3H); LC-MS: 411 (MH+).

Workup

  1. customThe reaction was quenched by water
  2. extractionextracted with dichloromethane
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. custompurified through silica gel chromatography

Sources & evidence

ORD record
ord-337b173f67df44678d75630cbed93f02
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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