Hydrochloric Acid → HCID 178519155, compound

HRID 1505688Notes

Reaction equation

HRID 1505688 reaction equation
N1([C:6](N2C=CN=C2)=[O:7])C=CN=C1.[I:13][C:14]1[CH:15]=[N:16][N:17]([CH:19]2[CH2:24][CH2:23][CH:22]([NH:25][CH2:26][CH2:27][OH:28])[CH2:21][CH2:20]2)[CH:18]=1.Cl>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[I:13][C:14]1[CH:15]=[N:16][N:17]([C@H:19]2[CH2:20][CH2:21][C@H:22]([N:25]3[CH2:26][CH2:27][O:28][C:6]3=[O:7])[CH2:23][CH2:24]2)[CH:18]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 899244402-[4-(4-Iodo-pyrazol-1-yl)-cyclohexylamino]-ethanol2×

Product 1

HCID 178519155HCID 178519155, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

Di-imidazol-1-yl-methanone (1.32 g; 8.14 mmol; 2.9 eq.) was added in one portion to a solution of 2-[4-(4-Iodo-pyrazol-1-yl)-cyclohexylamino]-ethanol (intermediate 25; 997 mg; 2.83 mmol; 1.0 eq.) and Dimethyl-pyridin-4-yl-amine (60 mg; 0.49 mmol; 0.17 eq.) in CHCl3 (30 mL). The reaction suspension was heated at 60° C. for 20 min then cooled and poured into a 1 N HCl solution. It was extracted with DCM (twice), combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM: MeOH; 96:4) followed by a trituration in Acetonitrile afforded the title compound as a white solid (239 mg; 23%). 1H NMR (300 MHz, DMSO) δ 7.96 (d, J=0.5 Hz, 1H), 7.51 (d, J=0.5 Hz, 1H), 4.30-4.12 (m, 3H), 3.63-3.46 (m, 3H), 2.11-2.00 (m, 2H), 1.91-1.58 (m, 6H). HPLC (Condition A): Rt 2.98 min (purity 99.0%). MS (ESI+): 362.2.

Workup

  1. temperaturethen cooled
  2. extractionIt was extracted with DCM (twice),
  3. washwere washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica (DCM: MeOH; 96:4)

Sources & evidence

ORD record
ord-8528fd4946944daf86d6694aaafbccf1
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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