Diisopropylethylamine → HCID 25099552, compound

HRID 2381917Notes

Reaction equation

HRID 2381917 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[C:4]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:3]=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.[F:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[N:54]([NH2:58])[CH2:53][C:52]2([CH3:60])[CH3:59]>CN(C=O)C.O.CCOC(C)=O>[F:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[N:54]([NH:58][C:8]([C:7]1[C:2]([CH3:1])=[N:3][C:4]([C:11]3[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=3)=[N:5][CH:6]=1)=[O:10])[CH2:53][C:52]2([CH3:60])[CH3:59]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 10571248(Dimethylamino)-N,N-dimethyl((1-oxo-1lambda~5~-pyridin-2-yl)sulfanyl)methaniminium hexafluorophosphateHCID 457912394-Methyl-2-(pyridin-3-yl)pyrimidine-5-carboxylic acidHCID 68555288HCID 68555288, compound

Product 1

HCID 25099552HCID 25099552, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-methyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid (706 mg, 3.28 mmol), HOTT (1.34 g, 3.6 mmol), and DIPEA (1.65 mL, 9.45 mmol) in DMF (15 mL) is stirred at rt under N2 for 10 min. 5-Fluoro-3,3-dimethyl-2,3-dihydro-indol-1-ylamine (560 mg, 3.11 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 35% EtOAc in heptane to afford 4-methyl-2-pyridin-3-yl-pyrimidine-5-carboxylic acid (5-fluoro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-amide (617 mg, 53%) as a solid. MS: 378 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 10.44 (s, 1H), 9.55-9.54 (m, 1H), 9.01 (s, 1H), 8.77-8.75 (m, 1H), 8.72-8.68 (m, 1H), 7.60 (dd, 1H), 7.06 (dd, 1H), 6.96-6.88 (m, 1H), 6.76-6.72 (m, 1H), 3.51 (s, 2H), 2.70 (s, 3H), 1.33 (s, 6H).

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 35% EtOAc in heptane

Sources & evidence

ORD record
ord-e87e01937d61452ba1c162fc8f622bb0
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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