Triethylamine → 2-chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonyloxymethyl)pyrimidine

HRID 1095411Notes

Reaction equation

HRID 1095411 reaction equation
ClC1N=C(CI)C=C(N2CCOC[C@@H]2C)N=1.[CH3:17][S:18](Cl)(=[O:20])=[O:19].[Cl:22][C:23]1[N:28]=[C:27]([CH2:29][OH:30])[CH:26]=[C:25]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][C@@H:32]2[CH3:37])[N:24]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:17][S:18]([O:30][CH2:29][C:27]1[CH:26]=[C:25]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][C@@H:32]2[CH3:37])[N:24]=[C:23]([Cl:22])[N:28]=1)(=[O:20])=[O:19]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 59380103(S)-4-(2-Chloro-6-(iodomethyl)pyrimidin-4-YL)-3-methylmorpholineHCID 59380181[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methanol

Product 1

HCID 593799762-chloro-4-[(3S)-3-methylmorpholin-4-yl]-6-(methylsulfonyloxymethyl)pyrimidineYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Chloro-4-(iodomethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine can also be prepared by the dropwise addition of methanesulfonyl chloride (91 mL, 1169.52 mmol) to [2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methanol (190 g, 779.68 mmol) and triethylamine (163 mL, 1169.52 mmol) in DCM (2293 mL) at 0° C. under air. The resulting solution was allowed to warm up slowly to RT over a period of 4 hours. The reaction mixture was quenched with water, extracted with DCM and the organic layer dried over MgSO4, filtered and evaporated to afford [2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methyl methanesulfonate as a yellow gum (251 g). Sodium iodide (234 g, 1560.07 mmol) was added to this material in acetone (3679 mL) and the resulting suspension stirred at RT for 16 hours. The reaction mixture was evaporated to dryness and redissolved in DCM and washed three times with water then with a saturated aqueous solution of sodium thiosulphate. The organic layer was dried over MgSO4, filtered and evaporated to afford crude desired product (270 g). This was purified by chromatography to give an off white solid which was further triturated with ether to give the desired material which was identical to previous samples.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with DCM
  3. dry with materialthe organic layer dried over MgSO4
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-0248d93d7340494596d51a0de96ca756
Source dataset
uspto-grants-2012_03
Patent number
US08138183B2

Reaction notes

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