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Diisopropylethylamine → 2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine

HRID 510370
Notes
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Reaction equation

HRID 510370 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:23])[C:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:13]=3[CH3:22])=[C:6]2[N:5]=[C:4]([CH:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:3]=1.C(N(C(C)C)CC)(C)C>C(O)C.O1CCOCC1.CN(C1C=CN=CC=1)C.C(OCC)(=O)C.Cl.C([Mo](C=O)(C=O)(C=O)(C=O)C=O)=O.[Pd]>[CH3:23][C:9]1[C:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:19])[F:20])[C:13]=2[CH3:22])=[C:6]2[N:5]=[C:4]([CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:3]=[CH:2][N:7]2[N:8]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

10

Reactant 2

HCID 81531DiisopropylethylamineHCID 867248677-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine

Product 1

HCID 712709062-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidineYield 21%

Reagents, catalysts & solvents 7

HCID 142844-(Dimethylamino)pyridineCatalyst
HCID 23938
Palladium
Catalyst
HCID 178521651HCID 178521651, compoundCatalyst
HCID 313Hydrochloric AcidSolvent
HCID 702EthanolSolvent
HCID 8857Ethyl AcetateSolvent
HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a suspension of 7-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine (85 mg, 0.201 mmol) in ethanol (2 mL) and 1,4-dioxane (2 mL) were added hexaformylmolybdenum (27.1 mg, 0.100 mmol), Pd/C (1.0 mg, mmol) and DMAP (49 mg, 0.4 mmol) and diisopropylethylamine (26 mg, 0.2 mmol). The reaction mixture was irradiated (microwave) and stirred at 150° C. for 15 minutes. Reaction mixture was cooled down, diluted with ethyl acetate (30 mL) and 5% HCl solution. Two layers were separated. Organic layer was dried and concentrated to dryness. The crude product was purified to yield the titled compound (16 mg, 21%); LC/MS: MS (ES+) m/e 390 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.70-1.81 (m, 4H) 2.28 (s, 3H) 2.45-2.49 (m, 3H) 2.96 (s, 1H) 3.37-3.47 (m, 3H) 3.92 (br. s., 2H) 4.10 (s, 2H) 6.89 (d, J=7.33 Hz, 1H) 7.34 (s, 1H) 7.52 (s, 1H) 8.86 (d, J=7.33 Hz, 1H).

Workup

  1. customThe reaction mixture was irradiated (microwave)
  2. customReaction mixture
  3. temperaturewas cooled down
  4. customTwo layers were separated
  5. customOrganic layer was dried
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-c4db10e524ce4300b50de26441c49bd1
Source dataset
uspto-grants-2015_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09096605B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes