Sodium Carbonate → 5-(1-Ethylpiperidin-4-yloxy)-3-isopropenyl-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 1888528Notes

Reaction equation

HRID 1888528 reaction equation
C1(S([N:10]2[C:14]3[CH:15]=[N:16][C:17]([C:28]#[N:29])=[C:18]([O:19][CH:20]4[CH2:25][CH2:24][N:23]([CH2:26][CH3:27])[CH2:22][CH2:21]4)[C:13]=3[C:12]3[CH:30]=[C:31](Br)[CH:32]=[N:33][C:11]2=3)(=O)=O)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[C:41](B1OC(C)(C)C(C)(C)O1)([CH3:43])=[CH2:42]>C1COCC1.C(=O)([O-])O.[Na+].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]>[CH2:26]([N:23]1[CH2:24][CH2:25][CH:20]([O:19][C:18]2[C:13]3[C:12]4[CH:30]=[C:31]([C:41]([CH3:43])=[CH2:42])[CH:32]=[N:33][C:11]=4[NH:10][C:14]=3[CH:15]=[N:16][C:17]=2[C:28]#[N:29])[CH2:21][CH2:22]1)[CH3:27]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 582668389-Benzenesulfonyl-3-bromo-5-(1-ethyl-piperidin-4-yloxy)-9H-dipyrido[2,3-b:4',3'-d]pyrrole-6-carbonitrile

Product 1

HCID 582668425-(1-Ethylpiperidin-4-yloxy)-3-isopropenyl-9H-dipyrido[2,3-b;4',3'-d]pyrrole-6-carbonitrileYield 165.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

9-Benzenesulfonyl-3-bromo-5-(1-ethyl-piperidin-4-yloxy)-9H-dipyrido[2,3-b:4′,3′-d]pyrrole-6-carbonitrile (147 mg, 0.272 mmol) and [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (11 mg, 0.014 mmol) were dissolved in THF (9 mL) and 1N aqueous sodium carbonate (3 mL) added followed by isopropenylboronic acid pinacol ester (0.076 mL, 0.408 mmol) and placed under an argon atmosphere. The reaction mixture was heated under microwave irradiation at 140° C. for 50 min. The cooled reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted into ethyl acetate (4×20 mL). The combined organic phase was washed with brine (20 mL), dried over sodium sulfate and concentrated in vacuo to afford the title compound as a brown solid (163 mg) which was used without further purification in the next step. 1H NMR (CDCl3, 300 MHz): 12.05 (br s, 1H), 8.81 (d, J=2.2 Hz, 1H), 8.77 (s, 1H), 8.64 (d, J=2.2 Hz, 1H), 5.48 (s, 1H), 5.28-5.24 (m, 1H), 5.09-4.97 (m, 1H), 3.02-2.91 (m, 2H), 2.49 (q, J=7.2 Hz, 2H), 2.35-2.20 (m, 7H), 2.19-2.07 (m, 2H), 1.12 (t, J=7.2 Hz, 3H).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted into ethyl acetate (4×20 mL)
  3. washThe combined organic phase was washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a9dd71d5b974ea2a9f1dd5efd658b49
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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