Water → Tert-butyl (4-{4-[(isopropylsulfonyl)methyl]-6-morpholin-4-ylpyrimidin-2-yl}phenyl)carbamate

HRID 2353662Notes

Reaction equation

HRID 2353662 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[C:4]([CH2:14][S:15]([CH:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[N:3]=1.O.[C:22]([O:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.C(COC)OC.C(O)C>[CH:18]([S:15]([CH2:14][C:4]1[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:7]=[C:2]([C:33]2[CH:32]=[CH:31][C:30]([NH:29][C:27](=[O:28])[O:26][C:22]([CH3:24])([CH3:23])[CH3:25])=[CH:35][CH:34]=2)[N:3]=1)(=[O:17])=[O:16])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 3613184(4-Boc-Aminophenyl)Boronic AcidHCID 593801124-(2-Chloro-6-(isopropylsulfonylmethyl)pyrimidin-4-yl)morpholine

Product 1

HCID 59380012Tert-butyl (4-{4-[(isopropylsulfonyl)methyl]-6-morpholin-4-ylpyrimidin-2-yl}phenyl)carbamate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

4-{2-Chloro-6-[(isopropylsulfonyl)methyl]pyrimidin-4-yl}morpholine (1.5 g, 4.69 mmol) was dissolved in a solution of 18% DMF in a mixture of 7:3:2 dimethoxyethane:water:ethanol (36 mL). {4-[(Tert-butoxycarbonyl)amino]phenyl}boronic acid (1.67 g, 7.04 mmol), 2M sodium carbonate solution (12 mL) and dichlorobis(triphenylphosphine) palladium catalyst (165 mg, 0.23 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 oil was dissolved in DCM and filtered to remove insoluble material. A brown solid precipitated from the filtrates and the filtrates were filtered again. The solid was analysed and found to be the desired material (1.9 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. dissolutionThe crude oil was dissolved in DCM
  7. filtrationfiltered
  8. customto remove insoluble material
  9. customA brown solid precipitated from the filtrates
  10. filtrationthe filtrates were filtered again

Sources & evidence

ORD record
ord-de9bdd23f0d9435cb597d03518986758
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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