Diisopropylethylamine → 1-(4-Amino-3,5-difluorophenyl)-8-[(3-chloroisonicotinoyl)amino]-4,5-dihydro-1h-benzo[g]indazole-3-carboxamide

HRID 457333

Reaction equation

HRID 457333 reaction equation
[NH2:1][C:2]1[CH:26]=[CH:25][C:5]2[CH2:6][CH2:7][C:8]3[C:9]([C:22]([NH2:24])=[O:23])=[N:10][N:11]([C:13]4[CH:18]=[C:17]([F:19])[C:16]([NH2:20])=[C:15]([F:21])[CH:14]=4)[C:12]=3[C:4]=2[CH:3]=1.[Cl:27][C:28]1[CH:36]=[N:35][CH:34]=[CH:33][C:29]=1[C:30](O)=[O:31].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:20][C:16]1[C:15]([F:21])=[CH:14][C:13]([N:11]2[C:12]3[C:4]4[CH:3]=[C:2]([NH:1][C:30](=[O:31])[C:29]5[CH:33]=[CH:34][N:35]=[CH:36][C:28]=5[Cl:27])[CH:26]=[CH:25][C:5]=4[CH2:6][CH2:7][C:8]=3[C:9]([C:22]([NH2:24])=[O:23])=[N:10]2)=[CH:18][C:17]=1[F:19]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27358163-Chloropyridine-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 222915298-Amino-1-(4-amino-3,5-difluorophenyl)-4,5-dihydro-1h-benzo[g]indazole-3-carboxamide

Product 1

HCID 222915091-(4-Amino-3,5-difluorophenyl)-8-[(3-chloroisonicotinoyl)amino]-4,5-dihydro-1h-benzo[g]indazole-3-carboxamideYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of the product from step 3 (0.75 g, 0.0021 mol) and 3-chloroisonicotinic cid (0.33 g, 0.0023 mol) in 20 mL of DMF was added 1 mL of diisopropylethylamine, followed by the addition of HATU (0.9 g, 0.0023 mol). The reaction was stirred at room temperature for 16 h and concentrated. The crude was purified by reverse phase HPLC to give 0.15 g of 1-(4-amino-3,5-difluorophenyl)-8-[(3-chloroisonicotinoyl)amino]-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide as a pale white solid (15% yield); 1HNMR (DMSO, 400 MHz) δ: 10.56 (s, 1H), 8.76 (s, 1H), 8.63 (d, 1H), 8.56 (s, 1H), 7.54 (d, 1H), 7.49 (dd, 1H), 7.35 (m, 2H), 7.31 (s, 1H), 6.71 (m, 2H), 5.88 (s, 2H), 2.92 (m, 4H); Anal. Calcd. for C24H17FClN6O2+0.5H2O: C, 57.21; H, 3.60; N, 16.68. Found: C, 56.91; H, 3.70; N, 16.64.

Workup

  1. concentrationconcentrated
  2. customThe crude was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-51a8e724cb5c4401ae36db3c1ffed2fc
Source dataset
uspto-grants-2007_03
Patent number
US07186743B2

Linked notes

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