Triethylamine → 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-N-[2-(dimethylamino)ethyl]-1H-indazole-3-carboxamide

HRID 218482Notes

Reaction equation

HRID 218482 reaction equation
[C:1]([C:3]1[CH:8]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[C:12]3[C:18]([OH:20])=O)[C:7]([C:21]#[N:22])=[C:6]([CH3:23])[NH:5][C:4]=1[CH3:24])#[N:2].CCN(CC)CC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:56][N:57]([CH3:61])[CH2:58][CH2:59][NH2:60]>CN(C=O)C>[C:1]([C:3]1[CH:8]([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][N:13]=[C:12]3[C:18]([NH:60][CH2:59][CH2:58][N:57]([CH3:61])[CH3:56])=[O:20])[C:7]([C:21]#[N:22])=[C:6]([CH3:23])[NH:5][C:4]=1[CH3:24])#[N:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 66053N,N-DimethylethylenediamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 249594695-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-3-carboxylic acid

Product 1

HCID 249598365-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-N-[2-(dimethylamino)ethyl]-1H-indazole-3-carboxamideYield 33.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-1H-indazole-3-carboxylic acid (300 mg, 0.94 mmol), from Synthetic Example 3, in DMF (5 mL) was added Et3N (476 mg, 4.7 mmol) and HATU (430 mg, 1.13 mmol). The mixture was stirred at rt for 30 min, then N,N-dimethylethylenediamine (167.2 mg, 1.9 mmol) was added. The mixture was kept at rt overnight, and then quenched with water. The reaction mixture was extracted with CH2Cl2, dried, and concentrated. The residue was purified by flash chromatography followed by HPLC to afford 5-(3,5-dicyano-1,4-dihydro-2,6-dimethyl-4-pyridinyl)-N-[2-(dimethylamino)ethyl]-1H-indazole-3-carboxamide (121 mg, 33.7%) (Cpd. No. 103.2, Table 2). 1H-NMR (400 MHz, DMSO-D6): δ=8.16 (s, 1H), 7.63 (d, 1H), 7.41 (d, 1H), 4.55 (s, 1H), 3.82 (t, 2H), 3.43 (t, 2H), 3.01 (s, 6H), 2.14 (s, 6H) ppm.

Workup

  1. waitThe mixture was kept at rt overnight
  2. customquenched with water
  3. extractionThe reaction mixture was extracted with CH2Cl2
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-d7e486abfe0b4033ac7c87a0a18f9804
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Reaction notes

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