Potassium Carbonate → HCID 117778627, compound

HRID 1527031Notes

Reaction equation

HRID 1527031 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 palladiumdichloride (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-9704d71c789d4043ae6b9c064c65313c
Source dataset
uspto-grants-2015_07
Patent number
US09085583B2

Reaction notes

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