Water → HCID 178464305, compound

HRID 2274420Notes

Reaction equation

HRID 2274420 reaction equation
[NH2:1][C:2]1[C:3]([C:13]2[NH:14][C:15]3[CH:21]=[C:20]([NH:22][CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[C:19]([F:28])=[CH:18][C:16]=3[N:17]=2)=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:6]=1.[CH2:29]([N:31]([CH2:35][CH3:36])[C:32](Cl)=[O:33])[CH3:30].C(N(CC)C(C)C)(C)C.O>O1CCCC1>[CH3:27][N:25]([CH3:26])[CH2:24][CH2:23][NH:22][C:20]1[C:19]([F:28])=[CH:18][C:16]2[N:17]=[C:13]([C:3]3[C:2]([NH:1][C:32](=[O:33])[N:31]([CH2:35][CH3:36])[CH2:29][CH3:30])=[CH:6][N:5]([CH:7]4[CH2:12][CH2:11][CH2:10][CH2:9][O:8]4)[N:4]=3)[NH:14][C:15]=2[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6916Diethylcarbamoyl chlorideHCID 81531DiisopropylethylamineHCID 178483735HCID 178483735, compound

Product 1

HCID 178464305HCID 178464305, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 132 mg of N1-{2-[4-amino-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-3-yl]-6-fluoro-3H-benzimidazol-5-yl}-N2,N2-dimethylethane-1,2-diamine in 8 mL of tetrahydrofuran with 428 μL of diethylcarbamoyl chloride and 560 μL of N,N-diisopropylethylamine is heated at 55° C. for 48 hours. 15 mL of water are added and then the aqueous phase is extracted with 3×15 mL of ethyl acetate. The organic phases are washed with 2×15 mL of distilled water, dried over magnesium sulfate, filtered and concentrated under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge, with a 95/5 dichloromethane/-methanol eluent. 18 mg of 3-[3-[6-(2-dimethylaminoethylamino)-5-fluoro-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]-1,1-diethylurea are isolated in the form of a yellow resin. 1H NMR (400 MHz, DMSO-d6, δ in ppm), after addition of a drop of TFA-d1 (trifluoroacetic acid CF3COOD-d1) and of a drop of acetic acid-d4-(CD3OD-d4): 1.16 (t, J=7.5 Hz, 6H); 1.56 (m, 2H); 1.70 (m, 1H); 1.97 (m, 2H); 2.14 (m, 1H); 2.86 (s, 6H); 3.37 (m, 6H); 3.50 (t, J=6.5 Hz, 2H); 3.68 (m, 1H); 3.96 (m, 1H); 5.48 (broad d, J=10.0 Hz, 1H); 6.88 (d, J=7.5 Hz, 1H); 7.42 (d, J=11.0 Hz, 1H); 8.11 (s, 1H).

Workup

  1. extractionthe aqueous phase is extracted with 3×15 mL of ethyl acetate
  2. washThe organic phases are washed with 2×15 mL of distilled water
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum in a rotary evaporator
  6. customThe reaction crude
  7. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-12 cartridge, with a 95/5 dichloromethane/-methanol eluent

Sources & evidence

ORD record
ord-c10d714370a14a70bcc45829bb0393eb
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

Loading…