Hydrazine hydrate (1:1) → HCID 178433733, compound

HRID 510442Notes

Reaction equation

HRID 510442 reaction equation
[CH3:1][C:2]1[C:19]([CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)=[C:5]2[N:6]=[C:7]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:8]=[C:9]([C:10]([NH2:12])=O)[N:4]2[N:3]=1.COC(OC)[N:34]([CH3:36])C.O.[NH2:40]N>C(O)(=O)C>[CH3:1][C:2]1[C:19]([CH2:20][C:21]2[C:26]3[C:25](=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH:24]=[CH:23][CH:22]=2)=[C:5]2[N:6]=[C:7]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:8]=[C:9]([C:10]3[N:34]=[CH:36][NH:40][N:12]=3)[N:4]2[N:3]=1

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 71270697HCID 71270697, compound

Product 1

HCID 178433733HCID 178433733, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 2-methyl-5-(4-morpholinyl)-3-(1-naphthalenylmethyl)pyrazolo[1,5-a]pyrimidine-7-carboxamide (55 mg, 0.137 mmol) in N,N-dimethylformamide dimethyl acetal (2 mL, 14.94 mmol) was stirred at 105° C. for 3 days and concentrated to give the crude. To the crude was added Acetic Acid (2 mL) and hydrazine hydrate (0.047 mL, 0.959 mmol). The reaction mixture was heated at 100° C. for 1 h and concentrated. Brine (10 mL) and EtOAc (20 mL) was added in. The aqueous phase was extracted with EtOAc (20 mL×4). The organic phases were combined and concentrated. The crude was purified on silica column (EtOAc/Hexane: 10˜40%) to give the product (20 mg, 33%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.27 (s, 3H) 3.56-3.82 (m, 8H) 4.39 (s, 2H) 7.14 (s, 1H) 7.29-7.59 (m, 4H) 7.77 (d, J=8.08 Hz, 1H) 7.85-7.98 (m, 1H) 8.38-8.61 (m, 2H); LC/MS: MS (ES+) m/e 426.0 [M+H]+.

Workup

  1. concentrationconcentrated
  2. customto give the crude
  3. temperatureThe reaction mixture was heated at 100° C. for 1 h
  4. concentrationconcentrated
  5. additionBrine (10 mL) and EtOAc (20 mL) was added in
  6. extractionThe aqueous phase was extracted with EtOAc (20 mL×4)
  7. concentrationconcentrated
  8. customThe crude was purified on silica column (EtOAc/Hexane: 10˜40%)

Sources & evidence

ORD record
ord-ea32368e6c12409ba8f6dc72b9d7cf71
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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