Sodium Carbonate → HCID 178428242, compound

HRID 1626161Notes

Reaction equation

HRID 1626161 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:11][C:10]([CH:13]3[CH2:15][CH2:14]3)([F:12])[CH2:9]2)[CH:5]=[C:4]([Cl:16])[N:3]=1.[CH3:17][C:18]1[NH:22][N:21]=[C:20]([NH2:23])[CH:19]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:16][C:4]1[N:3]=[C:2]([NH:23][C:20]2[NH:21][N:22]=[C:18]([CH3:17])[CH:19]=2)[CH:7]=[C:6]([N:8]2[CH2:11][C:10]([CH:13]3[CH2:15][CH2:14]3)([F:12])[CH2:9]2)[CH:5]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 931461H-Pyrazol-3-amine, 5-methyl-HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59617901HCID 59617901, compound

Product 1

HCID 178428242HCID 178428242, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

Nitrogen was bubbled through a mixture of 2,6-Dichloro-4-(3-cyclopropyl-3-fluoroazetidine-1-yl)pyridine (1.0 g, 3.83 mmol), 5-methyl-1H-pyrazol-3-amine (0.7 g, 3.85 mmol), tris-(dibenzylideneacetone)dipalladium(0) (Pd2 dba3, 180 mg, 0.2 mmol), 9,9-dimethyl-4,5-bis(diphenyl-phosphino)xanthene (xantphos, 220 mg, 0.38 mmol), Na2CO3 (570 mg, 5.4 mmol), and 1,4-dioxane (12 mL) for about 15 minutes in a microwave vial. The vial was capped and heated in the microwave to 140° C. for 45 minutes and then to 170° C. for 15 minutes. The reaction mixture was filtered through Celite and rinsed with 1,4-dioxane. The solvent was removed under reduced pressure and the residue was dissolved in methanol/CH2Cl2 (1:1, 50 mL). Silica (2.5 g) was added and the solvents were removed under reduced pressure and the residue was brought on a column (100 mL silica in CH2Cl2/3% 2-propanol). The column was eluted with a gradient of 2-propanol (3-5%) in CH2Cl2. The fractions that contained the product (running with TLC RF=0.4 (SiO2, CH2Cl2/5% 2-propanol)) were pooled and concentrated to yield 450 mg (37%) of the title compound with 84/90% purity (HPLC, 215/254 nm). 1H-NMR (300 MHz, DMSO-d6): δ 11.74 (s, 1H); 9.02 (s, 1H); 6.38 (s, 1H); 5.88 (s, 1H); 5.84 (s, 1H); 3.94-3.78 (m, 4H); 2.15 (s, 3H); 1.42-1.03 (m, 1H); 0.62-0.57 (m, 2H); 0.44-0.40 (m, 2H) ppm.

Workup

  1. customThe vial was capped
  2. filtrationThe reaction mixture was filtered through Celite
  3. washrinsed with 1,4-dioxane
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue was dissolved in methanol/CH2Cl2 (1:1, 50 mL)
  6. additionSilica (2.5 g) was added
  7. customthe solvents were removed under reduced pressure
  8. washThe column was eluted with a gradient of 2-propanol (3-5%) in CH2Cl2
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2a2c14371b904f918a31ce8cde802be9
Source dataset
uspto-grants-2014_07
Patent number
US08785444B2

Reaction notes

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