Triethylamine → 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid (1-isoquinolin-3-yl-ethyl)-[(2S,3aS,7aS)-1-(octahydro-indol-2-yl)methyl]-amide

HRID 2220720Notes

Reaction equation

HRID 2220720 reaction equation
FC(F)(F)C(O)=O.[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([C:18](=O)[CH3:19])[N:9]=1.C(N(CC)CC)C.C(OC([N:35]1[C@@H:43]2[C@@H:38]([CH2:39][CH2:40][CH2:41][CH2:42]2)[CH2:37][C@H:36]1[CH2:44][NH2:45])=O)(C)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:60][O:61][C:62]1[C:67]2[O:68][C:69]([CH3:72])([CH3:71])[O:70][C:66]=2[CH:65]=[C:64]([C:73](Cl)=[O:74])[CH:63]=1>ClCCl>[CH:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[C:10]([CH:18]([N:45]([CH2:44][C@@H:36]2[CH2:37][C@H:38]3[C@H:43]([CH2:42][CH2:41][CH2:40][CH2:39]3)[NH:35]2)[C:73]([C:64]2[CH:63]=[C:62]([O:61][CH3:60])[C:67]3[O:68][C:69]([CH3:72])([CH3:71])[O:70][C:66]=3[CH:65]=2)=[O:74])[CH3:19])[N:9]=1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 5049666Sodium triacetoxyborohydrideHCID 58622131tert-butyl (2S,3aS,7aS)-2-(aminomethyl)-octahydro-1H-indole-1-carboxylateHCID 693137071-Isoquinolin-3-yl-ethanone trifluoroacetic acid saltHCID 714100777-Methoxy-2,2-dimethyl-2H-1,3-benzodioxole-5-carbonyl chloride

Product 1

HCID 586221727-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid (1-isoquinolin-3-yl-ethyl)-[(2S,3aS,7aS)-1-(octahydro-indol-2-yl)methyl]-amideYield 5.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Experimental conditions analogous to Example 1, from 0.19 g (0.68 mmol) of 1-isoquinolin-3-yl-ethanone trifluoroacetic acid salt (neutralized in situ with 95 μL (0.68 mmol) of triethylamine, 0.20 g (0.82 mmol) of (2S,3aS,7aS)-2-aminomethyl-octahydro-indole-1-carboxylic acid tert-butyl ester, 6 mL dichloromethane, and 0.21 g (1.02 mmol) of sodium triacetoxyborohydride. The benzoylation/deprotection steps were done using 284 μL (2.04 mmol) of triethylamine and 0.15 g (0.61 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride. The residue from the organic layer was purified using reverse phase HPLC, mobile phase with a gradient 15-80% acetonitrile in 50 min. The residue was dissolved in dichloromethane, washed with aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate and evaporated in vacuum to yield 17 mg of the product as the free base mixture of diastereoisomers. LC-MSD, m/z for C31H37N3O4 [M+H]+: 516.7, [M+2H]2+: 258.9. 1H NMR (400 MHz, CDCl3): δ 1.2-2.1 (m, 20 H), 3.0-4.0 (m, 7 H), 5.4-5.5 (m, 1 H), 6.7-6.8 (m, 1 H), 7.0-7.1 (m, 1 H), 7.4-7.9 (m, 4 H), 7.9-8.0 (m, 1 H), 9.2-9.3 (m, 1 H).

Workup

  1. customThe residue from the organic layer was purified
  2. customin 50 min
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with aqueous sodium bicarbonate
  5. dry with materialdried with anhydrous magnesium sulfate
  6. customevaporated in vacuum

Sources & evidence

ORD record
ord-6bd64e59ca5449aea9cd46c941ee8d38
Source dataset
uspto-grants-2008_08
Patent number
US07417062B2

Reaction notes

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