Hydrochloric Acid → HCID 178494714, compound

HRID 2070918Notes

Reaction equation

HRID 2070918 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][C:9]([NH:13][C:14]3[N:30]=[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([CH2:22][N:23]5[CH2:28][CH2:27][NH:26][C:25](=O)[CH2:24]5)[N:16]4[N:15]=3)=[CH:10][CH:11]=2)[NH:6][N:5]=1.Cl.[OH2:32]>C(O)C>[CH3:1][O:2][CH2:3][C:4]1[C:12]2[C:7](=[CH:8][C:9]([NH:13][C:14]3[N:30]=[C:17]4[CH:18]=[CH:19][CH:20]=[C:21]([CH2:22][N:23]5[CH2:28][CH2:27][NH:26][CH2:25][C:24]5=[O:32])[N:16]4[N:15]=3)=[CH:10][CH:11]=2)[NH:6][N:5]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 178494715HCID 178494715, compound

Product 1

HCID 178494714HCID 178494714, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

4-((2-(3-(Methoxymethyl)-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methyl)piperazin-2-one. 6 M HCl in water (0.410 mL, 2.459 mmol) was added to a stirred mixture of 4-((2-(3-(methoxymethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methyl)piperazin-2-one (0.132 g, 0.246 mmol) in ethanol (5 mL) at 60° C. The resulting mixture was stirred vigorously and heated at 60° C. under a reflux condenser under nitrogen for 12 h. The solvent was removed on a rotary evaporator. The residue was dissolved in hot DMSO, diluted with methanol, filtered, and purified using reverse-phase semi-preparatory HPLC (5-30% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 30 min). Fractions containing the desired product were loaded onto a Strata X—C ion exchange column from Phenomenex. The column was washed successively with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. The product came off with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator and dried under high vacuum at 45° C. to give the desired product (0.012 g, 0.030 mmol, 12% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 12.67 (s, 1H), 9.86 (s, 1H), 8.19 (d, J=1.17 Hz, 1H), 7.86 (s, 1H), 7.51-7.65 (m, 3H), 7.24 (dd, J=1.76, 8.79 Hz, 1H), 7.11 (d, J=7.03 Hz, 1H), 4.66 (s, 2H), 4.11 (s, 2H), 3.29 (s, 3H), 3.17-3.27 (m, 4H), 2.80 (t, J=5.27 Hz, 2H); MS (ESI) m/z 407.5 [M+1]+.

Workup

  1. customThe solvent was removed on a rotary evaporator
  2. dissolutionThe residue was dissolved in hot DMSO
  3. additiondiluted with methanol
  4. filtrationfiltered
  5. custompurified
  6. customreverse-phase semi-preparatory HPLC (5-30% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 30 min)
  7. additionFractions containing the desired product
  8. washThe column was washed successively with water, acetonitrile, methanol
  9. concentrationwas concentrated on a rotary evaporator
  10. customdried under high vacuum at 45° C.

Sources & evidence

ORD record
ord-09541f8416ab46ff8e66455835dfc40b
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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