2-Methylmorpholine--hydrogen chloride (1/1) → 4-(2,3-Dichlorobenzyl)-2-(2-methylmorpholino)thiazolo[4,5-d]pyrimidin-7(4H)-one

HRID 1958023Notes

Reaction equation

HRID 1958023 reaction equation
Cl.[CH3:2][CH:3]1[O:8][CH2:7][CH2:6][NH:5][CH2:4]1.[Cl:9][C:10]1[C:30]([Cl:31])=[CH:29][CH:28]=[CH:27][C:11]=1[CH2:12][N:13]1[C:18]2[N:19]=[C:20](S(C)(=O)=O)[S:21][C:17]=2[C:16](=[O:26])[N:15]=[CH:14]1>C(N(CC)CC)C.CN(C=O)C.O>[Cl:9][C:10]1[C:30]([Cl:31])=[CH:29][CH:28]=[CH:27][C:11]=1[CH2:12][N:13]1[C:18]2[N:19]=[C:20]([N:5]3[CH2:6][CH2:7][O:8][CH:3]([CH3:2])[CH2:4]3)[S:21][C:17]=2[C:16](=[O:26])[N:15]=[CH:14]1

Participants

6

Reactant 2

HCID 226055572-Methylmorpholine--hydrogen chloride (1/1)HCID 667800974-(2,3-Dichlorobenzyl)-2-(methylsulfonyl)thiazolo[4,5-d]pyrimidin-7(4H)-one

Product 1

HCID 667798264-(2,3-Dichlorobenzyl)-2-(2-methylmorpholino)thiazolo[4,5-d]pyrimidin-7(4H)-oneYield 38.1%

Reagents, catalysts & solvents 3

HCID 8471TriethylamineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of triethylamine (2 drops), 2-methylmorpholine hydrochloride (16 mg, 0.154 mmol) and 4-(2,3-dichlorobenzyl)-2-(methylsulfonyl)thiazolo[4,5-d]pyrimidin-7(4H)-one (20 mg, 0.051 mmol) in DMF was stirred at 60° C. for 1 h. After cooled to ambient temperature, the mixture was diluted with water (10 mL) and extracted with dichloromethane (15 mL×3). The combined organic layers were washed with saturated brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (DCM:MeOH=20:1 elution) to give the desired product (8 mg, 38%) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ 8.49 (s, 1H), 7.63 (d, J=7.2 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.16 (s, J=6.9 Hz, 1H), 5.46 (s, 2H), 3.88 (dd, J=12.3, 2.7 Hz, 1H), 3.77 (br, 2H), 3.55-3.47 (m, 2H), 3.31-3.20 (m, 1H), 2.94-2.89 (m. 1H), 1.13 (d, J=5.7 Hz, 3H); LC-MS: 411 (MH+); IR (thin film): 2976, 2920, 2855, 2360, 1627, 1605, 1555, 1495, 1444 cm−1.

Workup

  1. temperatureAfter cooled to ambient temperature
  2. extractionextracted with dichloromethane (15 mL×3)
  3. washThe combined organic layers were washed with saturated brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (DCM:MeOH=20:1 elution)

Sources & evidence

ORD record
ord-afee6425f9b34f269005c1f607dc6cd3
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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