2-Chloropyrimidine-5-carboxylic acid → HCID 53235488, compound
Reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[CH:4][N:3]=1.O.[Cl-].[CH3:13][O:14]C1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[NH2:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C@H:39]2[CH2:43][O:42][C:41]([NH2:44])=[N:40]2)=[CH:33][CH:32]=1>CO>[NH2:44][C:41]1[O:42][CH2:43][C@H:39]([CH2:38][CH2:37][C:34]2[CH:35]=[CH:36][C:31]([NH:30][C:8]([C:5]3[CH:6]=[N:7][C:2]([O:14][CH3:13])=[N:3][CH:4]=3)=[O:10])=[CH:32][CH:33]=2)[N:40]=1Participants
Conditions
- Temperature
- 0 °C
Procedure
2-Chloro-pyrimidine-5-carboxylic acid (23 mg) was dissolved in methanol (1 ml) and the solution cooled to 0° C. before addition of 4-(4,6-dimethoxy[1.3.5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (45 mg). The reaction mixture was stirred for 5 minutes at 0° C. before dropwise addition of a solution of (S)-4-[2-(4-Amino-phenyl)-ethyl]-4,5-dihydro-oxazol-2-ylamine (30 mg) in methanol (1 ml). Stirring at 0° C. was continued for 1 hour before quenching by addition of a 1N solution of sodium hydroxide. The reaction mixture was then extracted three times with ethyl acetate and the combined organic layers washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by preparative HPLC to give 2-methoxy-pyrimidine-5-carboxylic acid {4-[2-((S)-2-amino-4,5-dihydro-oxazol-4-yl)-ethyl]-phenyl}-amide (9 mg) as a yellow solid. MS (ISP): 342.2 ([M+H]+).
Workup
- custombefore quenching by addition of a 1N solution of sodium hydroxide
- extractionThe reaction mixture was then extracted three times with ethyl acetate
- washthe combined organic layers washed with brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified by preparative HPLC
Sources & evidence
- ORD record
- ord-4df9e28cc3e54c5a8131f9b1b451080c
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08354441B2
Reaction notes
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