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

HRID 2381910Notes

Reaction equation

HRID 2381910 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[CH:12][C:11]([C:14]([OH:16])=O)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.C1C=NC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:51][C:52]1[CH:53]=[C:54]2[C:58](=[CH:59][CH:60]=1)[N:57]([NH2:61])[C:56]([CH3:62])=[CH:55]2.CCN(C(C)C)C(C)C>CN(C=O)C.O.CCOC(C)=O>[F:51][C:52]1[CH:53]=[C:54]2[C:58](=[CH:59][CH:60]=1)[N:57]([NH:61][C:14]([C:11]1[CH:12]=[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:16])[C:56]([CH3:62])=[CH:55]2

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450733632-(3-Fluorophenyl)pyrimidine-5-carboxylic acidHCID 685544085-Fluoro-2-methyl-indol-1-ylamine

Product 1

HCID 250995162-(3-Fluoro-phenyl)-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)amideYield 47%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (389 mg, 1.78 mmol), HOAt (290 mg, 2.13 mmol), and HATU (811 mg, 2.13 mmol) in DMF (20 mL) is stirred at rt under N2 for 20 min. 5-Fluoro-2-methyl-indol-1-ylamine (290 mg, 1.77 mmol) and DIPEA (450 μL, 2.58 mmol) are 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 25% DCM in heptane to afford 2-(3-fluoro-phenyl)-pyrimidine-5-carboxylic acid (5-fluoro-2-methyl-indol-1-yl)amide (300 mg, 47%) as a solid. MS: 365 (M+H). 1H NMR (300 MHz, CDCl3): δ 9.23 (s, 1H), 8.76 (s, 1H), 8.35-8.22 (m, 2H), 7.54-7.45 (m, 1H), 7.19-6.86 (m, 5H), 6.25 (s, 1H), 2.29 (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 25% DCM in heptane

Sources & evidence

ORD record
ord-866b65cbb5aa42948af720386014fc68
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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