Potassium Carbonate → HCID 117778627, compound

HRID 2206544Notes

Reaction equation

HRID 2206544 reaction equation
[CH3:1][C:2]1[CH:3]([CH2:10][NH:11][C:12]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27](Br)[CH:26]=3)[CH3:24])[C:15]=2[CH3:32])=[O:13])[C:4](=[O:9])[N:5]=[C:6]([CH3:8])[CH:7]=1.Cl[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][N:35]=1.C(=O)([O-])[O-].[K+].[K+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([CH:23]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:34]3[CH:39]=[CH:38][N:37]=[CH:36][N:35]=3)[CH:26]=2)[CH3:24])[C:15]=1[CH3:32])=[O:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 6428344-ChloropyrimidineHCID 117779497HCID 117779497, compound

Product 1

HCID 117778627HCID 117778627, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Procedure

A round bottom flask was charged with a magnetic stir bar, 1-[1-(3-Bromo-phenyl)-ethyl]-2-methyl-1H-indole-3-carboxylic acid (4,6-dimethyl-2-oxo-2,3-dihydro-pyridin-3-ylmethyl)-amide (Step 8) (20 mg, 0.04 mmol), 4-Chloro-pyrimidine (6.95 mg, 0.06 mmol), potassium carbonate (10.9 mg, 0.08 mmol), 1,1′-Bis(diphenylphosphino)ferrocene palladium dichloride (44 mg, 0.06 mmol) and 1,4-dixoane/H2O (4:1, 8 mL). The mixture was purged and placed under N2 and stirred heated to reflux with stirring overnight. The reaction was then allowed to cool to rt and the mixture was concentrated in vacuo. The resulting residue was purified by preparative-HPLC (Column: YMC-Actus Triart C18150*30 mm*5 um; Mobile phase A: water with 0.1% HCl solution; Mobile phase B: MeCN; column temperature: 30° C.; Gradient: 35-65% B). The collected fractions were combined and lyophilized to afford the title compound (6.3 mg, yield 35%) LCMS (M+H+) m/z: calc'd 491.23. found 492.0; 1H NMR (400 MHz, MeOD-d4) δ 9.2 (s, 1H), 8.85-8.54 (d, 2H), 8.14-8.06 (m, 2H), 7.78-7.72 (m, 1H), 7.58-7.54 (t, 1H), 7.44-7.42 (d, 1H), 7.15-7.12 (d, 1H), 7.04-7.01 (t, 2H), 7.01-6.79 (t, 1H), 6.8 (s, 1H), 6.14-6.12 (t, 1H), 4.88 (m, 2H), 4.67 (s, 1H), 2.73 (s, 3H), 2.6 (s, 3H), 2.47 (s, 3H), 2.08-2.07 (d, 3H).

Workup

  1. additionA round bottom flask was charged with a magnetic stir bar
  2. customThe mixture was purged
  3. temperatureheated
  4. temperatureto reflux
  5. stirringwith stirring overnight
  6. concentrationthe mixture was concentrated in vacuo
  7. customThe resulting residue was purified by preparative-HPLC (Column: YMC-Actus Triart C18150*30 mm*5 um; Mobile phase A: water with 0.1% HCl solution; Mobile phase B: MeCN; column temperature: 30° C.; Gradient: 35-65% B)

Sources & evidence

ORD record
ord-721b05704b984db8a6727a53f622a371
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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