Diisopropylethylamine → HCID 25099554, compound

HRID 2381919Notes

Reaction equation

HRID 2381919 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.[Cl:49][C:50]1[CH:51]=[C:52]2[C:56](=[CH:57][CH:58]=1)[N:55]([NH2:59])[C:54]([CH3:60])=[CH:53]2>CN(C=O)C.O.CCOC(C)=O>[Cl:49][C:50]1[CH:51]=[C:52]2[C:56](=[CH:57][CH:58]=1)[N:55]([NH:59][C:15]([C:11]1[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]=1)=[O:17])[C:54]([CH3:60])=[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 68555157HCID 68555157, compound

Product 1

HCID 25099554HCID 25099554, compoundYield 16%

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 (379 mg, 1.63 mmol), HOTT (662 mg, 1.78 mmol), and DIPEA (800 μL, 4.58 mmol) in DMF (10 mL) is stirred at rt under N2 for 10 min. 5-Chloro-2-methyl-indol-1-ylamine (274 mg, 1.52 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 triturated in ether to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (5-chloro-2-methyl-indol-1-yl)-amide (93 mg, 16%) as a solid. MS: 395 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 11.83 (s, 1H), 9.27 (s, 1H), 8.33 (d, 1H), 8.20-8.15 (m, 1H), 7.69-7.61 (m, 1H), 7.56 (d, 1H), 7.50-7.43 (m, 2H), 6.36 (s, 1H), 2.78 (s, 3H), 2.37 (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 triturated in ether

Sources & evidence

ORD record
ord-d5bae53ca434405b9e695053ed9c06ab
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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