Water → N-((1S)-1-{[(1S,4S)-5-({5-[4-(dimethylamino)phenyl]-2-pyridinyl}carbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-2,2-dimethylpropyl)-1H-indole-2-carboxamide

HRID 2098468Notes

Reaction equation

HRID 2098468 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([N:10]2[CH2:15][C@@H:14]3[CH2:16][C@H:11]2[CH2:12][N:13]3[C:17]([C@@H:19]([NH:24][C:25]([C:27]2[NH:28][C:29]3[C:34]([CH:35]=2)=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:9])=[N:6][CH:7]=1.[CH3:36][N:37]([CH3:47])[C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:36][N:37]([CH3:47])[C:38]1[CH:43]=[CH:42][C:41]([C:2]2[CH:3]=[CH:4][C:5]([C:8]([N:10]3[CH2:15][C@@H:14]4[CH2:16][C@H:11]3[CH2:12][N:13]4[C:17]([C@@H:19]([NH:24][C:25]([C:27]3[NH:28][C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])=[O:9])=[N:6][CH:7]=2)=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27343444-(Dimethylamino)phenylboronic acidHCID 67072574N-[(1S)-1-({(1S,4S)-5-[(5-bromo-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)-2,2-dimethylpropyl]-1H-indole-2-carboxamide

Product 1

HCID 67072396N-((1S)-1-{[(1S,4S)-5-({5-[4-(dimethylamino)phenyl]-2-pyridinyl}carbonyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]carbonyl}-2,2-dimethylpropyl)-1H-indole-2-carboxamideYield 41.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-[(1S)-1-({(1S,4S)-5-[(5-bromo-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)-2,2-dimethylpropyl]-1H-indole-2-carboxamide (100 mg, 0.186 mmol), [4-(dimethylamino)phenyl]boronic acid (31 mg, 0.186 mmol), Pd(Ph3P)4 (10 mg, 0.009 mmol), potassium carbonate (26 mg, 0.186 mmol) in toluene (6 mL), ethanol (2 mL), and water (0.5 mL) was heated to 80° C. for 10 h under a nitrogen atmosphere. The solution was concentrated and the resulting residue was purified by reverse phase HPLC. Concentration of the desired fractions containing product afforded the title compound (45 mg) as a pale brown solid. LCMS (m/z): 579.3 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm: 0.90-1.20 (m, 9H), 1.80-2.20 (m, 2H), 2.90-3.15 (m, 6H), 3.50-4.20 (m, 4H), 4.60-5.60 (m, 4H), 6.90-7.70 (m, 9H), 7.80-8.10 (m, 2H), 8.60-8.85 (m, 1H), 9.15-9.45 (m, 1H)

Workup

  1. concentrationThe solution was concentrated
  2. customthe resulting residue was purified by reverse phase HPLC
  3. additionConcentration of the desired fractions containing product

Sources & evidence

ORD record
ord-ec96b4c40347467db827b491ba9c8357
Source dataset
uspto-grants-2013_05
Patent number
US08450484B2

Reaction notes

Loading…