4-Nitro-1-(oxan-2-yl)-1H-pyrazole-3-carbaldehyde → HCID 136397089, compound

HRID 2274405Notes

Reaction equation

HRID 2274405 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:20])[C:5]([NH2:19])=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[N+:21]([C:24]1[C:25]([CH:35]=O)=[N:26][N:27]([CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:28]=1)([O-:23])=[O:22]>CO>[F:1][C:2]1[C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[CH:6][C:5]2[N:19]=[C:35]([C:25]3[C:24]([N+:21]([O-:23])=[O:22])=[CH:28][N:27]([CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][O:30]4)[N:26]=3)[NH:20][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 224778374-Nitro-1-(oxan-2-yl)-1H-pyrazole-3-carbaldehydeHCID 68842872HCID 68842872, compound

Product 1

HCID 136397089HCID 136397089, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 74 mg of 4-fluoro-5-(4-piperidin-1-ylbutoxy)benzene-1,2-diamine and 50.7 mg of 4-nitro-1-(tetrahydropyran-2-yl)-1H-pyrazole-3-carbaldehyde in 4 mL of methanol is stirred at ambient temperature for 18 hours. After evaporation of the solvent under reduced pressure in a rotary evaporator, the reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-4 cartridge with a dichloromethane/methanol eluent of 100% to 82/18. 77 mg of 6-fluoro-2-[4-nitro-1-(tetrahydropyran-2-yl)-1H-pyrazol-3-yl]-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazoleare isolated in the form of a yellow foam. 1H NMR (300 MHz, DMSO-d6, δ in ppm) for this batch, we observe a 60%-40% resolution of tautomers with: from 1.29 to 2.44 (m, 22H); 3.70 (m, 1H); 4.00 (m, 1H) 4.10 (t, J=6.0 Hz, 2H); 5.60 (dd, J=3.0 and 10.0 Hz, 1H); 7.21 (d, J=8.5 Hz, 0.6H); from 7.36 to 7.46 (m, 0.8H); 7.53 (d, J=11.0 Hz, 0.6H); 9.17 (s, 1H); 12.8 (broad s, 0.6H); 12.9 (broad s, 0.4H).

Workup

  1. customAfter evaporation of the solvent under reduced pressure
  2. customin a rotary evaporator
  3. customthe reaction crude
  4. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-4 cartridge with a dichloromethane/methanol eluent of 100% to 82/18
  5. custom77 mg of 6-fluoro-2-[4-nitro-1-(tetrahydropyran-2-yl)-1H-pyrazol-3-yl]-5-(4-piperidin-1-ylbutoxy)-1H-benzimidazoleare isolated in the form of a yellow foam

Sources & evidence

ORD record
ord-67c1c7c2bf7444aba852a4cbae692e77
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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