Water → Tert-butyl (4-{4-[(3S)-3-methylmorpholin-4-yl]-6-[(phenylsulfonyl)methyl]pyrimidin-2-yl}phenyl)carbamate

HRID 2353658Notes

Reaction equation

HRID 2353658 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][C@@H:9]2[CH3:14])[CH:5]=[C:4]([CH2:15][S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:18])=[O:17])[N:3]=1.O.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[CH:36][CH:35]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(COC)OC.C(O)C>[CH3:14][C@H:9]1[CH2:10][O:11][CH2:12][CH2:13][N:8]1[C:6]1[CH:5]=[C:4]([CH2:15][S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:18])=[O:17])[N:3]=[C:2]([C:34]2[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[CH:38][CH:39]=2)[N:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 2734617tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamateHCID 593800404-(benzenesulfonylmethyl)-2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidine

Product 1

HCID 59379956Tert-butyl (4-{4-[(3S)-3-methylmorpholin-4-yl]-6-[(phenylsulfonyl)methyl]pyrimidin-2-yl}phenyl)carbamateYield 67.9%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

(3S)-4-{2-Chloro-6-[(phenylsulfonyl)methyl]pyrimidin-4-yl}-3-methylmorpholine (3.2 g, 8.70 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2 dimethoxyethane:water:ethanol (36 mL). Tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]carbamate (4.16 g, 13.05 mmol), 2M sodium carbonate solution (8 mL) and dichlorobis(triphenylphosphine) palladium catalyst (306 mg, 0.43 mmol) were then added and the reaction refluxed at 90° C. for 2 hours under a nitrogen atmosphere. The reaction was allowed to cool to room temp then partitioned between ethyl acetate (20 mL) and water (20 mL). The organics were dried over magnesium sulphate, filtered and concentrated in vacuo. The crude solid was chromatographed on silica, eluting with 0-30% ethyl acetate in DCM to give the desired material as a beige solid (3.1 g).

Workup

  1. temperatureto cool to room temp
  2. customthen partitioned between ethyl acetate (20 mL) and water (20 mL)
  3. dry with materialThe organics were dried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude solid was chromatographed on silica
  7. washeluting with 0-30% ethyl acetate in DCM

Sources & evidence

ORD record
ord-63201f23f7734ddeab8b64a73db931d8
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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