Dimethyl Sulfoxide → 7-(Aminomethyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 64295Notes

Reaction equation

HRID 64295 reaction equation
[NH2:1][CH2:2][CH:3]1[N:8]2[N:9]=[C:10]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:16][CH:15]=3)[C:11]([C:12]#[N:13])=[C:7]2[NH:6][CH2:5][CH2:4]1.CS(C)=[O:29].[OH-].[Na+].OO>CCO>[NH2:1][CH2:2][CH:3]1[N:8]2[N:9]=[C:10]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:16][CH:15]=3)[C:11]([C:12]([NH2:13])=[O:29])=[C:7]2[NH:6][CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 136928071HCID 136928071, compound

Product 1

HCID 1369280997-(Aminomethyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamideYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 7-(aminomethyl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carbonitrile (15 mg, 0.043 mmol) in 2 mL of EtOH was added 1 mL of DMSO, 0.5 mL of NaOH (5N) and 0.5 mL of H2O2 (30% aqueous solution). After stirring at 60° C. for 2 hr, the mixture was concentrated to remove EtOH. The residue was partitioned between water (30 mL) and EA (20 mL). The organic phase was concentrated and purified by pre-HPLC eluting from 20% to 40% CH3CN in 0.1% TFA in H2O. Fractions containing the desired product were combined and lyophilized overnight to give the product as a TFA salt (10 mg, 64%). 1H NMR (400 MHz, DMSO-d6) δ 8.07 (br s, 3H), 7.62 (d, J=8.8 Hz, 2H), 7.43-7.35 (m, 2H), 7.25 (t, J=7.6 Hz, 1H), 7.15-7.12 (m, 4H), 6.77 (br s, 1H), 4.38-4.30 (m, 1H), 3.40-3.20 (m, 4H), 2.16-2.06 (m, 1H), 2.00-1.80 (m, 1H). MS (ESI) m/e [M+1]+364.0.

Workup

  1. concentrationthe mixture was concentrated
  2. customto remove EtOH
  3. customThe residue was partitioned between water (30 mL) and EA (20 mL)
  4. concentrationThe organic phase was concentrated
  5. custompurified
  6. washby pre-HPLC eluting from 20% to 40% CH3CN in 0.1% TFA in H2O
  7. additionFractions containing the desired product
  8. waitlyophilized overnight

Sources & evidence

ORD record
ord-4434afa9eac44a7d8209931b9f813b14
Source dataset
uspto-grants-2016_09
Patent number
US09447106B2

Reaction notes

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