Diisopropylethylamine → HCID 25099553, compound

HRID 2381918Notes

Reaction equation

HRID 2381918 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([CH3:14])[C:11]([C:15]([OH:17])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.CN(C(SC1[N+]([O-])=CC=CC=1)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:49][C:50]1[N:51]([NH2:60])[C:52]2[C:57]([C:58]=1[CH3:59])=[CH:56][CH:55]=[CH:54][CH:53]=2>CN(C=O)C.O.CCOC(C)=O>[CH3:49][C:50]1[N:51]([NH:60][C:15]([C:11]2[C:12]([CH3:14])=[N:13][C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)=[N:9][CH:10]=2)=[O:17])[C:52]2[C:57]([C:58]=1[CH3:59])=[CH:56][CH:55]=[CH:54][CH:53]=2

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 10571248(Dimethylamino)-N,N-dimethyl[(1-oxo-1lambda~5~-pyridin-2-yl)sulfanyl]methaniminium hexafluorophosphateHCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 68554528HCID 68554528, compound

Product 1

HCID 25099553HCID 25099553, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (764 mg, 3.29 mmol), HOTT (1.33 g, 3.58 mmol), and DIPEA (1.65 mL, 9.45 mmol) in DMF (15 mL) is stirred at rt under N2 for 10 min. 2,3-Dimethyl-indol-1-ylamine (497 mg, 3.1 mmol) is added. The resulting mixture is stirred at 80° 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 20% EtOAc in heptane to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (2,3-dimethyl-indol-1-yl)-amide (568 mg, 49%) as a solid. MS: 375 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 11.68 (s, 1H), 9.24 (s, 1H), 8.33 (d, 1H), 8.20-8.15 (m, 1H), 7.69-7.61 (m, 1H), 7.50-7.43 (m, 2H), 7.37 (d, 1H), 7.17-7.05 (m, 2H), 2.78 (s, 3H), 2.30 (s, 3H), 2.24 (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 20% EtOAc in heptane

Sources & evidence

ORD record
ord-891ed0e6d6764518945510a7c500435b
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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