Water → 1-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(1,2-oxazol-3-yl)urea

HRID 2353691Notes

Reaction equation

HRID 2353691 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]2[CH3:16])[N:3]=1.O.[O:18]1[CH:22]=[CH:21][C:20]([NH:23][C:24](=[O:41])[NH:25][C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)=[N:19]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.COCCOC.C(O)C>[OH:9][CH2:8][C:6]1[CH:5]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][C@@H:11]2[CH3:16])[N:3]=[C:2]([C:29]2[CH:28]=[CH:27][C:26]([NH:25][C:24]([NH:23][C:20]3[CH:21]=[CH:22][O:18][N:19]=3)=[O:41])=[CH:31][CH:30]=2)[N:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 593799953-(1,2-Oxazol-3-yl)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ureaHCID 59380181[2-chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methanol

Product 1

HCID 593800101-[4-[4-(hydroxymethyl)-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-2-yl]phenyl]-3-(1,2-oxazol-3-yl)ureaYield 37.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

[2-Chloro-6-[(3S)-3-methylmorpholin-4-yl]pyrimidin-4-yl]methanol (500 mg) was dissolved in an 18% DMF in a mixture of 7:3:2 DME:water:ethanol (10 mL). 3-(1,2-Oxazol-3-yl)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea (811 mg) and 2M aqueous sodium carbonate solution (4 mL) were then added to the solution and the resultant mixture degassed for 5 min. Dichlorobis(triphenylphosphine) palladium catalyst (73 mg) was added and the solution refluxed at 90° C. for 7 h under nitrogen atmosphere. The reaction was allowed to cool then neutralised with concentrated hydrochloric acid and loaded directly onto a SCX-2 column (50 g), the column was washed with methanol and the product eluted with 7N ammonia in methanol. The material was further purified by chromatography on silica, eluting with 5% methanol in DCM, to give the desired material (318 mg) as a white solid.

Workup

  1. customthe resultant mixture degassed for 5 min
  2. additionDichlorobis(triphenylphosphine) palladium catalyst (73 mg) was added
  3. temperatureto cool
  4. washthe column was washed with methanol
  5. washthe product eluted with 7N ammonia in methanol
  6. customThe material was further purified by chromatography on silica
  7. washeluting with 5% methanol in DCM

Sources & evidence

ORD record
ord-8fa997a814404087ac61fd2ecfd7b6f6
Source dataset
uspto-grants-2010_07
Patent number
US07750003B2

Reaction notes

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