Methanesulfonyl chloride → HCID 178505319, compound

HRID 1819473Notes

Reaction equation

HRID 1819473 reaction equation
[N+:1]([C:4]1[C:5]([NH:23][CH2:24][C@@H:25]2[CH2:30][CH2:29][C@H:28]([OH:31])[CH2:27][CH2:26]2)=[N:6][C:7]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]([F:22])([F:21])[F:20])=[N:8][CH:9]=1)([O-:3])=[O:2].[CH3:32][S:33](Cl)(=[O:35])=[O:34].C(N(C(C)C)CC)(C)C>C(Cl)Cl>[N+:1]([C:4]1[C:5]([NH:23][CH2:24][C@@H:25]2[CH2:30][CH2:29][C@H:28]([O:31][S:33]([CH3:32])(=[O:35])=[O:34])[CH2:27][CH2:26]2)=[N:6][C:7]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[O:18][C:19]([F:22])([F:21])[F:20])=[N:8][CH:9]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 178526827HCID 178526827, compound

Product 1

HCID 178505319HCID 178505319, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

cis-4-{[5-Nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexanol (3.6 g, 8.16 mmol) was dissolved in dry DCM (150 mL) and cooled to 5° C. Methanesulfonyl chloride (0.94 ml, 12.2 mmol) and diisopropylethylamine (4.26 ml, 24.4 mmol) were added sequentially. After 2 h, the reaction was quenched with cold water (10 mL) and warmed to room temperature. The solution was partitioned between DCM (100 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to yield a yellow solid. The residue was then chromatographed (silica, 100:1 DCM/MeOH) and washed with cold methanol to yield a pale yellow solid as methanesulfonic acid cis-4-{[5-nitro-2-(2-trifluoromethoxy-benzylamino)-pyrimidin-4-ylamino]-methyl}-cyclohexyl ester (3.90 g, 7.50 mmol, 92%).

Workup

  1. customthe reaction was quenched with cold water (10 mL)
  2. temperaturewarmed to room temperature
  3. customThe solution was partitioned between DCM (100 mL) and water (50 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with DCM (2×100 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a yellow solid
  11. customThe residue was then chromatographed (silica, 100:1 DCM/MeOH)
  12. washwashed with cold methanol

Sources & evidence

ORD record
ord-41e436110e5f46db8519629755cd889f
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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