Potassium Carbonate → HCID 178433732, compound

HRID 510444Notes

Reaction equation

HRID 510444 reaction equation
Cl[C:2]1[N:7]2[N:8]=[C:9]([CH3:22])[C:10]([CH2:11][C:12]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH:15]=[CH:14][CH:13]=3)=[C:6]2[N:5]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[CH:3]=1.[NH:29]1[CH:33]=[CH:32][C:31](B(O)O)=[N:30]1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:22][C:9]1[C:10]([CH2:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][CH:13]=2)=[C:6]2[N:5]=[C:4]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:3]=[C:2]([C:33]3[CH:32]=[CH:31][NH:30][N:29]=3)[N:7]2[N:8]=1

Participants

7

Reactant 3

HCID 11430Potassium Carbonate2×HCID 71532471HCID 71532471, compoundHCID 178514837HCID 178514837, compound3×

Product 1

HCID 178433732HCID 178433732, compoundYield 21.2%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalyst3×HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

In 5 mL MW vial was added in 7-chloro-2-methyl-5-(4-morpholinyl)-3-(1-naphthalenylmethyl)pyrazolo[1,5-a]pyrimidine (70 mg, 0.178 mmol), 1H-pyrazol-3-ylboronic acid (59.8 mg, 0.535 mmol), PdCl2(dppf)-CH2Cl2 adduct (17.46 mg, 0.021 mmol) and potassium carbonate (98 mg, 0.713 mmol) in 1,2-Dimethoxyethane (DME) (1.6 mL) and Water (0.400 mL). The reaction vessel was heated with microwave irradiation at 140° C. for 15 min. LC-MS showed 15% conversion. 1H-pyrazol-3-ylboronic acid (59.8 mg, 0.535 mmol) and PdCl2(dppf)-CH2Cl2 adduct (17.46 mg, 0.021 mmol) was added in. The reaction vessel was heated with microwave irradiation at 140° C. for 35 min. LC-MS showed 50% conversion. 1H-pyrazol-3-ylboronic acid (59.8 mg, 0.535 mmol), potassium carbonate (98 mg, 0.713 mmol) and PdCl2(dppf)-CH2Cl2 adduct (17.46 mg, 0.021 mmol) was added in. The reaction vessel was heated with microwave irradiation at 140° C. for 50 min. The reaction mixture was filtered through celite and washed with EtOAc (50 mL). The organic phase was washed with brine (10 mL). The aqueous phase was extracted with DCM (20 mL). The organic phases were combined, dried (MgSO4) and concentrated. The crude was purified on silica column (EtOAc/Hexane: 20˜40%) to give the product (16 mg, 20%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.26 (s, 3H) 3.61-3.79 (m, 8H) 4.38 (s, 2H) 7.12 (br. s., 1H) 7.33-7.46 (m, 2H) 7.46-7.53 (m, 2H) 7.57 (d, J=2.27 Hz, 1H) 7.76 (d, J=8.08 Hz, 1H) 7.86-8.00 (m, 2H) 8.46-8.55 (m, 1H). LC/MS: MS (ES+) m/e 425.0 [M+H]+.

Workup

  1. temperatureThe reaction vessel was heated with microwave irradiation at 140° C. for 35 min
  2. temperatureThe reaction vessel was heated with microwave irradiation at 140° C. for 50 min
  3. filtrationThe reaction mixture was filtered through celite
  4. washwashed with EtOAc (50 mL)
  5. washThe organic phase was washed with brine (10 mL)
  6. extractionThe aqueous phase was extracted with DCM (20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude was purified on silica column (EtOAc/Hexane: 20˜40%)

Sources & evidence

ORD record
ord-f6a51cd692b24608b7551e8843d1b2a3
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

Loading…