Hydrochloric Acid → HCID 178433734, compound

HRID 510443Notes

Reaction equation

HRID 510443 reaction equation
[CH3:1][C:2]1[C:19]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:22]=2[CH3:31])=[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:35]([CH3:37])C.O.[NH2:41]N.[OH-].[Na+].Cl>CCOC(C)=O.C1COCC1.C(O)(=O)C>[CH3:1][C:2]1[C:19]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[C:22]=2[CH3:31])=[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:12]=[CH:37][NH:35][N:41]=3)[N:4]2[N:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 78373Dimethylformamide dimethyl acetalHCID 71270913HCID 71270913, compound

Product 1

HCID 178433734HCID 178433734, compoundYield 48.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(4-morpholinyl)pyrazolo[1,5-a]pyrimidine-7-carboxamide (0.45 g, 1.038 mmol) in N,N-dimethylformamide dimethyl acetal (15 mL, 112 mmol) was stirred at 105° C. for 18 h. The reaction mixture was concentrated. To the crude material was added Acetic Acid (10 mL) and hydrazine monohydrate (0.228 mL, 7.27 mmol). The reaction mixture was heated at 100° C. for 1 h and concentrated. The crude material was purified on a silica column (EtOAc/Hexane: 20˜60%). The product is inseparable with the side product. To the mixture was added THF (30 mL) and sodium hydroxide (2.076 mL, 2.076 mmol). The reaction mixture was stirred at rt for 2 h. EtOAc (100 mL) was added in. The reaction was acidified with 1 N HCl. The aqueous phase was extracted with EtOAc (100 mL×2). The organic phases were combined, dried (MgSO4) and concentrated. The crude was purified on silica column (eluting with EtOAc/Hexane: 20˜60%) then (5% MeOH/DCM) to give the product (0.23 g, 46%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.27 (s, 3H) 2.46 (s, 3H) 3.50-3.76 (m, 8H) 4.00 (s, 2H) 7.13 (br. s., 1H) 7.21-7.33 (m, 1H) 7.41 (d, J=7.58 Hz, 1H) 7.52 (d, J=7.83 Hz, 1H) 8.54 (br. s., 1H) 14.55 (br. s., 1H); LC/MS: MS (ES+) m/e 458.2 [M+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. temperatureThe reaction mixture was heated at 100° C. for 1 h
  3. concentrationconcentrated
  4. customThe crude material was purified on a silica column (EtOAc/Hexane: 20˜60%)
  5. stirringThe reaction mixture was stirred at rt for 2 h
  6. extractionThe aqueous phase was extracted with EtOAc (100 mL×2)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude was purified on silica column (eluting with EtOAc/Hexane: 20˜60%)

Sources & evidence

ORD record
ord-1912e17a82254250807c68325920248d
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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