Hydrochloric Acid → HCID 16071904, compound

HRID 1043473Notes

Reaction equation

HRID 1043473 reaction equation
[F:1][CH:2]([F:33])[C:3]1[C:7]([C:8]2[NH:9][C:10]3[C:16]4[CH:17]=[CH:18][N:19]=[CH:20][C:15]=4[NH:14][C:13]4[N:21]=[CH:22][CH:23]=[CH:24][C:12]=4[C:11]=3[N:25]=2)=[C:6]([CH3:26])[N:5](C2CCCCO2)[N:4]=1.CO.Cl.C([O-])(O)=O.[Na+]>>[F:33][CH:2]([F:1])[C:3]1[C:7]([C:8]2[NH:9][C:10]3[C:16]4[CH:17]=[CH:18][N:19]=[CH:20][C:15]=4[NH:14][C:13]4[N:21]=[CH:22][CH:23]=[CH:24][C:12]=4[C:11]=3[N:25]=2)=[C:6]([CH3:26])[NH:5][N:4]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 668870762-[3-(difluoromethyl)-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b: 4',3'-f]azepine

Product 1

HCID 16071904HCID 16071904, compoundYield 80.1%

Conditions

Temperature
25 °C

Procedure

2-[3-(difluoromethyl)-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl]-3,8-dihydroimidazo[4,5-d]dipyrido[2,3-b:4′,3′-f]azepine (1.69 g, 3.76 mmol) was dissolved in methanol (50.00 mL, 1.234 mol) and concentrated HCl (2.00 mL) was added. The reaction was stirred at 25° C. for 20 h. The reaction was neutralized with NaHCO3 and was extracted with ethyl acetate and the organic extracts were washed with water, saturated NaCl, dried (MgSO4), concentrated in vacuo to a reduced volume and crystallized from MeOH/EtOAc to give the desired product (1.10 g). A portion of this (0.70 g) was suspended in methanol and 1.00 M of HCl in ether (6.00 mL) was added at which time the compound was completely dissolved. The reaction was concentrated in vacuo to reduce solvent to a minimal volume and ether was added. The crystallized solid was washed with ether and dried to give the bis hydrochloride salt (0.82 mg). Free base 1H NMR (DMSO-d6): δ 8.72 (br s, 1H), 8.14 (d, 1H), 8.01 (s, 1H), 7.95 (dd, 1H), 7.80 (m, 1H), 7.76 (d, 1H), 7.11-7.38 (t, 1H), 6.90 (dd, 1H), 2.48 (s, 3H). Mass spec (EI) m/z=366 (M+1).

Workup

  1. extractionwas extracted with ethyl acetate
  2. washthe organic extracts were washed with water, saturated NaCl
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo to a reduced volume
  5. customcrystallized from MeOH/EtOAc

Sources & evidence

ORD record
ord-0b35ac42242645ff8aa5c5913c80cb85
Source dataset
uspto-grants-2013_10
Patent number
US08563541B2

Reaction notes

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