Diisopropylethylamine → 2-Pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)-amide

HRID 2381893Notes

Reaction equation

HRID 2381893 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:12]=[CH:11][C:10]([C:13]([OH:15])=O)=[CH:9][N:8]=2)[CH:2]=1.CN(C(ON1N=NC2C=CC(=CC1=2)Cl)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[F:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[N:56]([NH2:60])[C:55]([CH3:61])=[CH:54]2>CN(C=O)C.O.CCOC(C)=O>[F:50][C:51]1[CH:52]=[C:53]2[C:57](=[CH:58][CH:59]=1)[N:56]([NH:60][C:13]([C:10]1[CH:11]=[N:12][C:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[N:8][CH:9]=1)=[O:15])[C:55]([CH3:61])=[CH:54]2

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 249036372-(Pyridin-3-YL)pyrimidine-5-carboxylic acidHCID 42624899O-(6-Chlorobenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphateHCID 685544085-Fluoro-2-methyl-indol-1-ylamine

Product 1

HCID 250994722-Pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)-amideYield 46%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (506 mg, 2.13 mmol), HCTU (970 mg, 2.34 mmol), and DIPEA (1 mL, 5.72 mmol) in DMF (10 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-2-methyl-indol-1-ylamine (311 mg, 1.89 mmol) is added. The resulting mixture is stirred at 75° C. overnight. The mixture is cooled and portioned between EtOAc and water. The organic phase is separated, washed with saturated aqueous NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 45% EtOAc in heptane to afford 2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)-amide (300 mg, 46%) as a solid. MS: 348 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 12.02 (s, 1H), 9.60 (d, 1H), 9.49 (s, 2H), 8.82-8.76 (m, 2H), 7.64 (dd, 1H), 7.39 (dd, 1H), 7.29 (dd, 1H), 6.94 (dt, 1H), 6.35 (s, 1H), 2.33 (s, 3H).

Workup

  1. temperatureThe mixture is cooled
  2. customThe organic phase is separated
  3. washwashed with saturated aqueous NaHCO3, water and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with 45% EtOAc in heptane

Sources & evidence

ORD record
ord-83bf278e786c4eac8acd7051b7e0e532
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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