Diisopropylethylamine → 2-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide

HRID 2382087Notes

Reaction equation

HRID 2382087 reaction equation
[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]([NH2:11])[CH:3]=1.[F:12][C:13]1[CH:14]=[C:15]([C:19]2[N:24]=[C:23]([CH3:25])[C:22]([C:26](O)=[O:27])=[CH:21][N:20]=2)[CH:16]=[CH:17][CH:18]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]([NH:11][C:26]([C:22]2[C:23]([CH3:25])=[N:24][C:19]([C:15]3[CH:16]=[CH:17][CH:18]=[C:13]([F:12])[CH:14]=3)=[N:20][CH:21]=2)=[O:27])[CH:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 617025872-(3-Fluorophenyl)-4-methylpyrimidine-5-carboxylic acidHCID 685552333-Methyl-pyrrolo[3,2-b]pyridin-1-yl amine

Product 1

HCID 592000172-(3-Fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amideYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-methyl-pyrrolo[3,2-b]pyridin-1-yl amine (75% pure) (240 mg, <1.63 mmol), 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (379 mg, 1.63 mmol), HATU (744 mg, 1.96 mmol) and DIPEA (388 mg, 4.89 mmol) in DMF (5 mL) is heated at 1500 C. for 1 h. The reaction is quenched with water, extracted with EtOAc. The organic layer is dried (Na2SO4), filtered and concentrated. The residue is chromatographed through silica gel eluting with 10% MeOH in DCM. The resulting product is recrystallized with ether to afford 2-(3-fluoro-phenyl)-4-methyl-pyrimidine-5-carboxylic acid (3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide (197 mg, 44%). MS: 362 (M+H); 1H NMR (300 MHz, CD3OD): δ 9.14 (s, 1H), 8.40 (d, 1H), 8.36 (d, 1H), 8.22 (d, 1H), 7.85(d, 1H), 7.55 (q 1H), 7.47 (s, 1H), 7.25-7.34 (m, 2H), 2.83 (s, 3H), 2.42(s, 3H). IC50=2 nM.

Workup

  1. temperatureis heated at 1500 C
  2. customThe reaction is quenched with water
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue is chromatographed through silica gel eluting with 10% MeOH in DCM
  8. customThe resulting product is recrystallized with ether

Sources & evidence

ORD record
ord-447c8fceb5db41f88cc55655dd544fe9
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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