1,2-Dichloroethane → N-[(1S)-2,2-dimethyl-1-({(1S,4S)-5-[(5-phenyl-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)propyl]-5-fluoro-1H-indole-2-carboxamide

HRID 2098466Notes

Reaction equation

HRID 2098466 reaction equation
[CH3:1][C:2]([CH3:29])([CH3:28])[C@H:3]([NH2:27])[C:4]([N:6]1[CH2:11][C@@H:10]2[CH2:12][C@H:7]1[CH2:8][N:9]2[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][N:16]=1)=[O:14])=[O:5].[F:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([C:40](O)=[O:41])=[CH:34]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(Cl)Cl>[CH3:1][C:2]([CH3:29])([CH3:28])[C@H:3]([NH:27][C:40]([C:35]1[NH:36][C:37]2[C:33]([CH:34]=1)=[CH:32][C:31]([F:30])=[CH:39][CH:38]=2)=[O:41])[C:4]([N:6]1[CH2:11][C@@H:10]2[CH2:12][C@H:7]1[CH2:8][N:9]2[C:13]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:17][N:16]=1)=[O:14])=[O:5]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 18205-Fluoroindole-2-carboxylic acidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 58286415[(1S)-2,2-dimethyl-1-({(1S,4S)-5-[(5-phenyl-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)propyl]amine

Product 1

HCID 67072196N-[(1S)-2,2-dimethyl-1-({(1S,4S)-5-[(5-phenyl-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)propyl]-5-fluoro-1H-indole-2-carboxamideYield 47.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of [(1S)-2,2-dimethyl-1-({(1S,4S)-5-[(5-phenyl-2-pyridinyl)carbonyl]-2,5-diazabicyclo[2.2.1]hept-2-yl}carbonyl)propyl]amine (100 mg, 0.25 mmol), 5-fluoro-1H-indole-2-carboxylic acid (48 mg, 0.26 mmol), EDC (58 mg, 0.3 mmol), HOBt (7 mg, 0.05 mmol), NMM (77 mg, 0.76 mmol) in CH2Cl2 (3 mL) was stirred at room temperature for 2 h. The mixture was washed with 1N sodium hydroxide (2×3 mL), water (2×10 mL). The combined aqueous washes were extracted with CH2Cl2 (2×5 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered concentrated to give the crude product, which was purified by reverse phase HPLC. Concentration of the desired fractions containing product afforded the title compound (66 mg) as a pale yellow solid. LCMS (m/z): 554.3 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm: 0.90-1.10 (m, 9H), 1.80-2.15 (m, 2H), 3.45-4.20 (m, 4H), 4.60-5.55 (m, 3H), 6.90-7.60 (m, 10H), 7.80-8.10 (m, 2H), 8.55-8.90 (m, 1H), 9.20-9.55 (m, 1H)

Workup

  1. washThe mixture was washed with 1N sodium hydroxide (2×3 mL), water (2×10 mL)
  2. extractionThe combined aqueous washes were extracted with CH2Cl2 (2×5 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product, which
  7. customwas purified by reverse phase HPLC
  8. additionConcentration of the desired fractions containing product

Sources & evidence

ORD record
ord-ad5af404b823492b8c8f6e22fb8dc0a2
Source dataset
uspto-grants-2013_05
Patent number
US08450484B2

Reaction notes

Loading…