Potassium Carbonate → HCID 59854604, compound

HRID 2375940Notes

Reaction equation

HRID 2375940 reaction equation
[Br:1][C:2]1[C:3]([NH:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][N:17]=[CH:16]3)=[C:4]2[CH:10]=[C:9](I)[NH:8][C:5]2=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:28]([O:32][C:33]([N:35]1[CH2:40][CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>>[C:28]([O:32][C:33]([N:35]1[CH2:36][CH:37]=[C:38]([C:9]2[NH:8][C:5]3=[N:6][CH:7]=[C:2]([Br:1])[C:3]([NH:12][C:13]4[CH:14]=[C:15]5[C:19](=[CH:20][CH:21]=4)[NH:18][N:17]=[CH:16]5)=[C:4]3[CH:10]=2)[CH2:39][CH2:40]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59854563HCID 59854563, compound

Product 1

HCID 59854604HCID 59854604, compound

Procedure

To a mixture of (5-bromo-2-iodo-1H-pyrrolo[2,3-b]pyridin-4-yl)-(1H-indazol-5-yl)-amine (25 mg, 0.069 mmol), potassium carbonate (19 mg, 0.14 mmol), tetrakistriphenylphosphine palladium (10 mg, 0.014 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (21.6 mg, 0.069 mmol) was added degassed DMF (3 mL) and water (0.75 mL) and the mixture was heated to reflux for 5 h. Water was added to the reaction and filtered. The precipitate was washed with water and the filtrate was extracted with DCM. The precipitate was dissolved in DCM/MeOH mixture (9:1) and combined with the DCM extract and evaporated. The crude product was purified by preparative TLC using 8% methanol in DCM as eluent to afford the title compound as beige solid. 1H NMR (400 MHz, CD3OD): δ=10.32 (s, 1H), 8.11 (s, 1H), 8.02 (s, 1H), 7.58 (d, J=0.8 Hz, 1H), 7.47 (d, J=8.9 Hz, 1H), 7.26 (dd, J=8.8, 1.9 Hz, 1H), 6.69 (s, 1H), 5.95 (bs, 1H), 5.16 (bs, 1H), 3.99-4.03 (m, 2H), 3.42 (t, J=5.4 Hz, 2H), 2.00-2.07 (m, 2H), 1.39 (s, 9H); MS (ES+): m/z 510.89 (100) [MH+]; HPLC: tR=2.63 min (ZQ2000, polar—5 min).

Workup

  1. additionwas added
  2. customdegassed DMF (3 mL) and water (0.75 mL)
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 5 h
  5. additionWater was added to the reaction
  6. filtrationfiltered
  7. washThe precipitate was washed with water
  8. extractionthe filtrate was extracted with DCM
  9. dissolutionThe precipitate was dissolved in DCM/MeOH mixture (9:1)
  10. extractionextract
  11. customevaporated
  12. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-20059043d7c6453a8b93c7e96e626909
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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