Sodium Carbonate → 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1H-pyrazol-4-yl)thieno[3,2-c]pyridin-4-amine

HRID 1909980Notes

Reaction equation

HRID 1909980 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29](I)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11].CC1(C)C(C)(C)OB([C:40]2[CH:41]=[N:42][N:43](C(OC(C)(C)C)=O)[CH:44]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH2:9][C:10]([N:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[C:25]4[C:26]([NH2:31])=[N:27][CH:28]=[C:29]([C:40]5[CH:41]=[N:42][NH:43][CH:44]=5)[C:24]=4[S:23][CH:22]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1)=[O:11]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 668236633-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine

Product 1

HCID 534676163-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1H-pyrazol-4-yl)thieno[3,2-c]pyridin-4-amineYield 34.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 25 mL microwave reactor pressure tube was charged 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-iodothieno[3,2-c]pyridin-4-amine (129 mg, 0.236 mmol), 1,1-dimethylethyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (69.3 mg, 0.236 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex 9.62 mg, 0.012 mmol), and saturated aqueous sodium carbonate (0.707 mL, 0.707 mmol) followed by dioxane (5 mL). The reaction was heated at 120° C. for 40 min in microwave reactor. The reaction was cooled to room temperature, the mixture was transfered into a 100 mL Erlenmeyer flask, rinsed by EtOAc, with the water layer and black greasy solid stayed in tube, total 100 mL of EtOAc was added to the mixture. The EtOAc solution was evaporated to dryness, and re-dissolved with CH2Cl2/MeOH (8 mL/2 mL). It was purified by flash column 25-100% EtOAc/hexane, then 0-10% MeOH/EtOAc, Si SF15-24g, to afford a brown solid. The brown solid was further purified by recrystallizaton in CH3CN to give the title compound 3-{1-[(2,5-difluorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-(1H-pyrazol-4-yl)thieno[3,2-c]pyridin-4-amine (40 mg) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.24-3.29 (m, 2H), 3.97 (s, 2H), 4.32 (t, J=8.46 Hz, 2H), 5.40 (s, 2H), 7.18-7.21 (m, 1H), 7.23-7.29 (m, 3H), 7.38 (s, 1H), 7.49 (s, 1H), 7.96 (s, 1H), 8.07 (s, 1H), 8.12 (d, J=8.34 Hz, 2H), 13.09 (s, 1H)

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. washrinsed by EtOAc, with the water layer and black greasy solid
  3. customstayed in tube
  4. additiontotal 100 mL of EtOAc was added to the mixture
  5. customThe EtOAc solution was evaporated to dryness
  6. dissolutionre-dissolved with CH2Cl2/MeOH (8 mL/2 mL)
  7. customIt was purified by flash column 25-100% EtOAc/hexane
  8. custom0-10% MeOH/EtOAc, Si SF15-24g, to afford a brown solid
  9. customThe brown solid was further purified by recrystallizaton in CH3CN

Sources & evidence

ORD record
ord-ef177e085eba4cf589331a2918d5c21c
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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