Water → HCID 58709765, compound

HRID 2375939Notes

Reaction equation

HRID 2375939 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:33][C:17]3=[N:18][CH:19]=[C:20](Br)[C:21]([NH:22][C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[NH:28][N:27]=[CH:26]5)=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[C:35](#[N:37])C>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.[Fe+2].[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:33][C:17]3=[N:18][CH:19]=[C:20]([C:35]#[N:37])[C:21]([NH:22][C:23]4[CH:24]=[C:25]5[C:29](=[CH:30][CH:31]=4)[NH:28][N:27]=[CH:26]5)=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 962WaterHCID 6342AcetonitrileHCID 59854604HCID 59854604, compound

Product 1

HCID 58709765HCID 58709765, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

To a mixture of 4-[5-bromo-4-(1H-indazol-5-ylamino)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (8 mg, 0.015 mmol), DPPF (4.1 mg, 0.007 mmol), water (0.03 mL) and zinc cyanide (3.7 mg, 0.031 mmol) in acetonitrile (3 mL) was added Pd2 dba3 (3.6 mg, 0.004 mmol) and the mixture was heated to reflux under N2 overnight. The reaction mixture was evaporated and the crude product was purified by preparative TLC using 10% methanol in DCM as eluent to afford 4-[5-cyano-4-(1H-indazol-5-ylamino)-1H-pyrrolo[2,3-b]pyridin-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester as light gray solid. 1H NMR (400 MHz, CD3OD): δ=8.05 (s, 1H), 7.96 (s, 1H), 7.62 (dd, J=1.8, 0.5 Hz, 1H), 7.50 (s, 1H), 7.27 (dd, J=8.8, 1.9 Hz, 1H), 6.05 (bs, 1H), 5.35 (bs, 1H), 3.93-3.97 (m, 2H), 3.40 (t, J=6.2 Hz, 2H), 2.02-2.07 (m, 2H), 1.37 (s, 9H); MS (ES+): m/z 455.99 (100) [MH+]; HPLC: tR=2.97 min (ZQ2000, polar—5 min).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under N2 overnight
  3. customThe reaction mixture was evaporated
  4. customthe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-26f0fafdb753466ab9be4279e755af97
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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