Diisopropylethylamine → N-{5-[1-({3-Cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}cyclopropanecarboxamide

HRID 2189875Notes

Reaction equation

HRID 2189875 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:17]([F:18])=[CH:16][C:13]([C:14]#[N:15])=[C:12](F)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.[NH2:20][CH:21]([C:23]1[CH:24]=[CH:25][C:26]([F:35])=[C:27]([NH:29][C:30]([CH:32]2[CH2:34][CH2:33]2)=[O:31])[CH:28]=1)[CH3:22].CCN(C(C)C)C(C)C>C(O)CCC>[C:14]([C:13]1[C:12]([NH:20][CH:21]([C:23]2[CH:24]=[CH:25][C:26]([F:35])=[C:27]([NH:29][C:30]([CH:32]3[CH2:34][CH2:33]3)=[O:31])[CH:28]=2)[CH3:22])=[N:11][C:10]([NH:9][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[NH:8][N:7]=2)=[C:17]([F:18])[CH:16]=1)#[N:15]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 674265316-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,5-difluoronicotinonitrileHCID 67427191HCID 67427191, compound

Product 1

HCID 67426455N-{5-[1-({3-Cyano-6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-5-fluoropyridin-2-yl}amino)ethyl]-2-fluorophenyl}cyclopropanecarboxamide

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
150 °C

Procedure

To a 10-ml microwave reaction vessel was added 6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2,5-difluoronicotinonitrile (Method 32, 431 mg, 1.65 mmol), N-[5-(1-aminoethyl) -2-fluorophenyl]cyclopropanecarboxamide (Method 69, 550 mg, 2.5 mmol), and DIEA (1.15 ml, 6.6 mmol) in n-butanol (5 ml). The resulting suspension was set to microwave heating (CEM Discover System) at 150° C. for 3 hours. The reaction was concentrated in vacuo and purified by silica gel chromatography (Biotage Horizon System) using a gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes to give 267 mg (35% isolated yield) of the title compound. 1H NMR: 11.99 (s, 1H) 9.91 (s, 1H) 9.42 (s, 1H) 7.88 (d, J=6.03 Hz, 1H) 7.59 (d, J=10.55 Hz, 1H) 6.95-7.20 (m, 3H) 5.99 (s, 1H) 5.02-5.21 (m, 1H) 1.89-2.03 (m, 1H) 1.76-1.89 (m, 1H) 1.45 (d, J=7.54 Hz, 3H) 0.87 (t, J=8.67 Hz, 2H) 0.75 (d, J=6.03 Hz, 4H) 0.54-0.66 (m, 2H). MS: Calcd.: 463. Found: [M+H]+ 464.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompurified by silica gel chromatography (Biotage Horizon System)
  3. washa gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes
  4. customto give

Sources & evidence

ORD record
ord-451a0ca9a86847d1a2a0a35681c8a564
Source dataset
uspto-grants-2012_12
Patent number
US08324252B2

Reaction notes

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