1-Butanol → HCID 67426482, compound

HRID 75914Notes

Reaction equation

HRID 75914 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.FC1C(NC2C=C(OC(C)C)NN=2)=NC([NH:30][C@H:31]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[CH3:32])=C([N+]([O-])=O)C=1.[CH3:50][CH2:51][N:52](C(C)C)C(C)C.C([OH:63])CCC>>[C:14]([C:13]1[C:12]([NH:30][CH:31]([C:33]2[CH:34]=[CH:35][C:36]([F:39])=[C:37]([NH:52][C:51](=[O:63])[CH3:50])[CH:38]=2)[CH3:32])=[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 4

HCID 2631-ButanolHCID 81531DiisopropylethylamineHCID 674265316-(5-cyclopropyl-1H-pyrazol-3-ylamino)-2,5-difluoronicotinonitrileHCID 178458650(S)-3-Fluoro-N6-(1-(4-fluorophenyl)ethyl)-N2-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyridine-2,6-diamine

Product 1

HCID 67426482HCID 67426482, compound

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, 300 mg, 1.13 mmol), N-[5-(1-aminoethyl)-2-fluorophenyl]acetamide (Method 66, 331 mg, 1.7 mmol), and DIEA (0.8 ml, 4.6 mmol) in n-butanol (4 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 180 mg (36% isolated yield) of the title compound. 1H NMR: 9.66 (br s, 1H) 9.43 (s, 1H) 7.81 (d, J=6.03 Hz, 2H) 7.60 (d, J=11.30 Hz, 1H) 6.92-7.21 (m, 3H) 5.98 (s, 1H) 5.13 (t, J=7.16 Hz, 1H) 2.05 (s, 3H) 1.76-1.92 (m, 1H) 1.46 (d, J=6.78 Hz, 3H) 0.82-0.95 (m, J=8.29 Hz, 2H) 0.54-0.66 (m, 2H). MS: Calcd.: 437. Found: [M+H]+ 438.

Workup

  1. additionTo a 10-ml microwave reaction vessel was added
  2. concentrationThe reaction was concentrated in vacuo
  3. custompurified by silica gel chromatography (Biotage Horizon System)
  4. washa gradient elution of 25-35% EtOAc (20% v/v MeOH) in hexanes
  5. customto give

Sources & evidence

ORD record
ord-99b4d4862ecd46c3859c5f7da30484fc
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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