Hydrochloric Acid → HCID 51354326, compound

HRID 2367277Notes

Reaction equation

HRID 2367277 reaction equation
CC([N:5]([CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:20]=[C:19]([C:21]3[CH:29]=[C:28]4[C:24]([C:25]([NH2:30])=[N:26][NH:27]4)=[CH:23][CH:22]=3)[N:18]=[C:17]([NH2:31])[N:16]=2)[CH2:10]1)C(=O)[O-])(C)C.[ClH:32]>>[ClH:32].[NH2:31][C:17]1[N:18]=[C:19]([C:21]2[CH:29]=[C:28]3[C:24]([C:25]([NH2:30])=[N:26][NH:27]3)=[CH:23][CH:22]=2)[CH:20]=[C:15]([N:11]2[CH2:12][CH2:13][CH2:14][CH:9]([NH2:5])[CH2:10]2)[N:16]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86762359HCID 86762359, compound

Product 2

HCID 313Hydrochloric AcidHCID 51354326HCID 51354326, compoundYield 115%

Procedure

1,1-Dimethylethyl{1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-3-piperidinyl}carbamate (865 mg, 2.04 mmol) was added portionwise to ice-cooled hydrochloric acid (concentrated aqueous) (8 mL, 96 mmol) with stirring. A solid yellow mass formed. The ice bath was removed and the reaction was allowed to warm to room temperature with stirring. HPLC indicated complete conversion. The mixture was diluted with ice-water (20 mL) and the solution was concentrated under reduced pressure. The residue was dissolve in ethanol (15 mL) and evaporated, followed by suspending in CH3CN (15 mL) and evaporating. The residue was then triturated with isopropanol (10 mL) and filtered, washed with isopropanol, followed by hexanes and dried under vacuum to afford an HCl salt of the title compound (761 mg) as a yellow powder. A 140 mg portion was suspended in CH3OH (2 mL) and water (1 mL) and was neutralized to pH 10 with 1 N NaOH. The solution was filtered and purified by Gilson automated reverse phase HPLC (Gemini Phenomenex C18 5u, 100×300 mm), eluting with 5-90% CH3CN-water+0.1% NH4OH). Pure fractions were combined, evaporated and dried to afford the title compound (72 mg) as a white solid. LC-MS (ES) m/z=325 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.15-1.29 (m, 1H), 1.31-1.46 (m, 1H), 1.51 (bs, 2H), 1.62-1.75 (m, 1H), 1.87 (d, J=10.6 Hz, 1H), 2.53-2.68 (m, 2H), 2.83 (t, J=12.1 Hz, 1H), 4.30 (m, 2H), 5.38 (s, 2H), 6.03 (bs, 2H), 6.58 (s, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.94 (s, 1H), 11.52 (s, 1H).

Workup

  1. customA solid yellow mass formed
  2. customThe ice bath was removed
  3. stirringwith stirring
  4. additionThe mixture was diluted with ice-water (20 mL)
  5. concentrationthe solution was concentrated under reduced pressure
  6. dissolutionThe residue was dissolve in ethanol (15 mL)
  7. customevaporated
  8. customevaporating
  9. customThe residue was then triturated with isopropanol (10 mL)
  10. filtrationfiltered
  11. washwashed with isopropanol
  12. customdried under vacuum

Sources & evidence

ORD record
ord-755b5dfbad2c43388f548f40e456dc1a
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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