Hydrochloric Acid → HCID 66601603, compound

HRID 604320Notes

Reaction equation

HRID 604320 reaction equation
[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:17]([N:22]4[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]4)=[N:18][CH:19]=[CH:20][CH:21]=3)[CH2:12][CH2:11]2)[CH:5]=[N:4]1)[CH3:2].[ClH:29]>C(O)C.C(OC)(C)(C)C>[ClH:29].[ClH:29].[CH2:1]([N:3]1[C:7]([CH3:8])=[C:6]([CH2:9][N:10]2[CH2:11][CH2:12][N:13]([C:16]3[C:17]([N:22]4[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]4)=[N:18][CH:19]=[CH:20][CH:21]=3)[CH2:14][CH2:15]2)[CH:5]=[N:4]1)[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 25227419HCID 25227419, compound

Product 1

HCID 66601603HCID 66601603, compoundYield 84.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
52.5 °C

Procedure

Dissolve 3′-[4-(1-Ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-piperazin-1-yl]-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-ol (415 g, 1.079 mol)) in ethanol (5.5 liters) and methyl t-butyl ether (6.23 liters). Stir the solution under a nitrogen atmosphere and heat to 50-55° C. Add 2.96 M HCl solution in ethanol (0.729 L) at 50-55° C. over 50 min. Allow the mixture to cool to about 40.1° C. over 90 min. Cool the mixture to 20° C. over 20 min., and then stir at 20° C. for 30 min. Filter the mixture and wash with methyl t-butyl ether (3×500 mL). Dry the solid in a vacuum oven at 50-55° C. under vacuum with a slight nitrogen sweep for 24 hr. to provide 3′-[4-(1-ethyl-5-methyl-1H-pyrazol-4-ylmethyl)-piperazin-1-yl]-3,4,5,6-tetrahydro-2H-[1,2]bipyridinyl-4-ol dihydrochloride (416 g, 84.3%). 1H NMR 500 MHz (CD3OD) δ 7.89 (dd, J=6.0 Hz, 2H), 7.828 (s, 1H), 7.275 (dd, J=6.0 Hz, 1H), 4.86 (CD3OH), 4.385 (s, 2H), 4.220 (q, J=7.1 Hz, 2H), 4.04 (bm, 2H), 3.976 (bm, 1H), 3.70 (bm, 4H), 3.511 (bm, 2H), 3.410 (bt, 2H), 3.145 (t, J=8.1, 2H), 2.467 (s, 3H), 2.082 (bm, 2H), 1.716 (bm, 2H), 1.416 (t, J=7.5 Hz, 3H). Chloride analysis is obtained by ICP/MS (15.6%).

Workup

  1. temperatureAllow the mixture to cool to about 40.1° C. over 90 min
  2. temperatureCool the mixture to 20° C. over 20 min.
  3. stirringstir at 20° C. for 30 min
  4. filtrationFilter the mixture
  5. washwash with methyl t-butyl ether (3×500 mL)
  6. customDry the solid in a vacuum oven at 50-55° C. under vacuum with a slight nitrogen sweep for 24 hr

Sources & evidence

ORD record
ord-e821679abed24629ba0dbe2b774bcffc
Source dataset
uspto-grants-2011_03
Patent number
US07910588B2

Reaction notes

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