4-Methylmorpholine → HCID 59200019, compound

HRID 2382027Notes

Reaction equation

HRID 2382027 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[N:3]=1.[Cl-].[F:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([NH3+:28])[CH:23]=[C:22]2[CH3:29].CN1CCOCC1.[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>O.CN(C=O)C>[F:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[N:24]([NH:28][C:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([C:11]3[N:16]=[CH:15][CH:14]=[CH:13][N:12]=3)=[N:5][CH:6]=1)=[O:10])[CH:23]=[C:22]2[CH3:29]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 616999854-Methyl-2-(pyrimidin-2-yl)pyrimidine-5-carboxylic acidHCID 68554956HCID 68554956, compound

Product 1

HCID 59200019HCID 59200019, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

4-Methyl-[2,2]bipyrimidinyl-5-carboxylic acid (0.5 g, 2.31 mmol) is combined with 5-fluoro-3-methyl-indol-1-yl-ammonium chloride (464 mg, 2.31 mmol), N-methylmorpholine (233 mg, 2.31 mmol) and DMF (10 mL). The suspension is stirred for 5 minutes at rt, then 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholin-4-ium chloride is added (640 mg, 2.31 mmol). The reaction is heated to 50° C. for 4 h. The reaction is then poured into water (50 mL), the suspension is chilled for 2 h in the refrigerator, and then filtered. The solids are then suspended in acetonitrile at 50° C. for 4 h, cooled, then filtered to afford 4-methyl-[2,2′]bipyrimidinyl-5-carboxylic acid (5-fluoro-3-methyl-indol-1-yl)-amide (60%). MS: 363 (M+H); 1H NMR (300 MHz, CDCl3): δ=2.27 (s, 3H), 2.77 (s, 3H), 7.07 (dt, 1H), 7.36 (dd, 1H), 7.38 (s, 1H), 7.44-7.48 (m, 1H), 7.70 (t, 1H), 9.05 (d, 2H), 9.29 (s, 1H), 11.9 (s, 1H). IC50=4.5 nM.

Workup

  1. temperatureThe reaction is heated to 50° C. for 4 h
  2. temperaturethe suspension is chilled for 2 h in the refrigerator
  3. filtrationfiltered
  4. waitThe solids are then suspended in acetonitrile at 50° C. for 4 h
  5. temperaturecooled
  6. filtrationfiltered

Sources & evidence

ORD record
ord-4847beb681424c52b8e712c5103b6283
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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