Diisopropylethylamine → HCID 25099656, compound

HRID 2381937Notes

Reaction equation

HRID 2381937 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.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.OC1C=CC2NN=NC=2N=1.[NH2:51][N:52]1[C:60]2[C:55](=[C:56]([F:61])[CH:57]=[CH:58][CH:59]=2)[CH:54]=[CH:53]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:61][C:56]1[CH:57]=[CH:58][CH:59]=[C:60]2[C:55]=1[CH:54]=[CH:53][N:52]2[NH:51][C:14]([C:11]1[CH:12]=[N:13][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[N:9][CH:10]=1)=[O:16]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 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 68553171HCID 68553171, compoundHCID 178515788HCID 178515788, compound

Product 1

HCID 25099656HCID 25099656, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of 2-(3-fluorophenyl)-pyrimidine-5-carboxylic acid (0.33 g), HATU (0.67 g) and hydroxyazabenzotriazole (0.26 g) in dry DMF (15 mL) is stirred at rt for 30 min under N2. A solution of 1-amino-4-fluoroindole (0.24 g) in dry DMF (5 mL) is added followed by the addition of DIPEA (0.39 mL). The mixture is stirred at 80° C. for 24 h, cooled to rt, and then concentrated in vacuo. The residue is dissolved in EtOAc and washed with water, brine and dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 60% DCM/heptane to afford 2-(3-fluorophenyl)pyrimidine-5-carboxylic acid-(4-fluoroindol-1-yl)amide (0.24 g, 53%) as a solid. MS: 351 (M+H); 1H NMR (300 MHz, DMSO-d6): δ 6.64 (d, 1H), 6.89-6.92 (q, 1H), 7.15-7.22 (m, 1H), 7.31-7.33 (d, 1H), 7.46-7.52 (m, 1H), 7.56 (d, 1H), 7.63-7.70 (q, 1H), 8.18-8.23 (d, 1H), 8.34-8.37 (d, 1H), 9.45 (s, 2H), 12.30 (s, 1H). IC50=11 nM.

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with water, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel chromatography
  9. washeluting with 60% DCM/heptane

Sources & evidence

ORD record
ord-28edf2cbaa5049d38d7808add7400c82
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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