Diisopropylethylamine → HCID 25099550, compound

HRID 2381915Notes

Reaction equation

HRID 2381915 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.[NH2:49][N:50]1[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[C:52]([C:59](=[O:64])[C:60]([F:63])([F:62])[F:61])=[CH:51]1>CN(C=O)C.O.CCOC(C)=O>[F:63][C:60]([F:61])([F:62])[C:59]([C:52]1[C:53]2[C:58](=[CH:57][CH:56]=[CH:55][CH:54]=2)[N:50]([NH:49][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])[CH:51]=1)=[O:64]

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 68552103HCID 68552103, compound

Product 1

HCID 25099550HCID 25099550, compoundYield 11.5%

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 (360 mg, 1.55 mmol), HOTT (628 mg, 1.69 mmol), and DIPEA (740 μL, 4.24 mmol) in DMF (10 mL) is stirred at rt under N2 for 10 min. 1-(1-Amino-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (322 mg, 1.4 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 HPLC reverse phase column chromatography eluting with a mobile phase of 0.1% TFA/water through 100% MeCN in a 30 min. ramp to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid [3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-amide (71 mg, 11%) as a solid. MS: 443 (M+H). 1H NMR (300 MHz, DMSO-d6): δ 12.56 (s, 1H), 9.32 (s, 1H), 8.90 (d, 1H), 8.35 (d, 1H), 8.30-8.27 (m, 1H), 8.22-8.17 (m, 1H), 7.75-72 (m, 1H), 7.69-7.62 (m, 1H), 7.52-7.44 (m, 3H), 2.81 (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 HPLC reverse phase column chromatography
  8. washeluting with a mobile phase of 0.1% TFA/water through 100% MeCN in a 30 min. ramp

Sources & evidence

ORD record
ord-7fd974921aed4ce2a0373796a1194dd8
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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