4-Fluoro-5-morpholin-4-ylbenzene-1,2-diamine → HCID 178526865, compound

HRID 2274382Notes

Reaction equation

HRID 2274382 reaction equation
[N+:1]([C:4]1[C:5]([CH:15]=O)=[N:6][N:7](C2CCCCO2)[CH:8]=1)([O-:3])=[O:2].[F:17][C:18]1[CH:19]=[C:20]([NH2:31])[C:21]([NH2:30])=[CH:22][C:23]=1[N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>CO>[F:17][C:18]1[C:23]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)=[CH:22][C:21]2[N:30]=[C:15]([C:5]3[C:4]([N+:1]([O-:3])=[O:2])=[CH:8][NH:7][N:6]=3)[NH:31][C:20]=2[CH:19]=1

Participants

4

Reactant 2

HCID 15103004-Fluoro-5-morpholin-4-ylbenzene-1,2-diamineHCID 224778374-Nitro-1-(oxan-2-yl)-1H-pyrazole-3-carbaldehyde

Product 1

HCID 178526865HCID 178526865, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
22 °C

Procedure

530 mg of 4-nitro-1-(tetrahydropyran-2-yl)-1H-pyrazole-3-carbaldehyde (the preparation of which is described in WO 03/035065, reference example 6m page 479) are added slowly to a solution of 500 mg of 4-fluoro-5-morpholin-4-ylbenzene-1,2-diamine in 50 mL of methanol, and then 19.5 mg of ferric chloride are added. The reaction medium is stirred at 22° C. for 18 hours. After evaporation, the reaction crude is purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-90 cartridge. The elution is carried out as follows: 100% cyclohexane for 20 minutes, then 20 minutes with an 80:20 cyclohexane/ethyl acetate mixture and 120 minutes with a 20:80 cyclohexane/ethyl acetate mixture. 457 mg of 6-fluoro-5-morpholin-4-yl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzimidazoleare isolated. 1H NMR (400 MHz, (CD3)2SO, δ in ppm): 1.42-1.80 (m: 3H); 1.91-2.06 (m: 2H); 2.18 (m: 1H); 3.02 (m: 4H); 3.70 (m: 1H); 3.78 (m: 4H); 4.00 (broad d J=10 Hz: 1H); 5.60 (dd, J=10 and 2 Hz: 1H); 7.18 (very broad s: 1H); 7.45 (very broad s: 1H); 9.18 (s: 1H); 12.85 (very broad s: 1H).

Workup

  1. customAfter evaporation
  2. customthe reaction crude
  3. customis purified by flash chromatography on an Intelliflash apparatus on an Analogix RS-90 cartridge
  4. washThe elution
  5. wait100% cyclohexane for 20 minutes
  6. custom20 minutes
  7. customwith an 80:20 cyclohexane/ethyl acetate mixture and 120 minutes
  8. custom457 mg of 6-fluoro-5-morpholin-4-yl-2-(4-nitro-1H-pyrazol-3-yl)-1H-benzimidazoleare isolated

Sources & evidence

ORD record
ord-2824996e1dfd4acda47dbeb543760b1c
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

Loading…