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

HRID 2220708Notes

Reaction equation

HRID 2220708 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[C@@H:23]2[C@@H:18]([CH2:19][CH2:20][CH2:21][CH2:22]2)[CH2:17][C@H:16]1[CH2:24][NH:25][CH2:26][C:27]1[O:28][C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[CH:31]=1)=O)(C)(C)C.C(N(CC)CC)C.[CH3:43][O:44][C:45]1[C:50]2[O:51][C:52]([CH3:55])([CH3:54])[O:53][C:49]=2[CH:48]=[C:47]([C:56](Cl)=[O:57])[CH:46]=1.FC(F)(F)C(O)=O>ClCCl>[O:28]1[C:29]2[CH:35]=[CH:34][CH:33]=[CH:32][C:30]=2[CH:31]=[C:27]1[CH2:26][N:25]([CH2:24][C@@H:16]1[CH2:17][C@H:18]2[C@H:23]([CH2:22][CH2:21][CH2:20][CH2:19]2)[NH:15]1)[C:56]([C:47]1[CH:46]=[C:45]([O:44][CH3:43])[C:50]2[O:51][C:52]([CH3:55])([CH3:54])[O:53][C:49]=2[CH:48]=1)=[O:57]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 69308401(2s,3As,7as)-2-{[(benzofuran-2-ylmethyl)-amino]-methyl}-octahydro-indole-1-carboxylic acid tert-butyl ester trifluoroacetic acid saltHCID 714100777-Methoxy-2,2-dimethyl-2H-1,3-benzodioxole-5-carbonyl chloride

Product 1

HCID 586222447-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid benzofuran-2-ylmethyl-[(2S,3aS,7aS)-1-(octahydro-indol-2-yl)methyl]-amideYield 29.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 45 mg (0.09 mmol) of (2S,3aS,7aS)-2-{[(benzofuran-2-ylmethyl)-amino]-methyl}-octahydro-indole-1-carboxylic acid tert-butyl ester trifluoroacetic acid salt in 1 mL dichloromethane, 28 μL (0.20 mmol) of triethylamine and 23 mg (0.10 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride were added at r.t. Stirring at r.t. for 1 hour was followed by the addition of 0.1 mL trifluoroacetic acid; 2 hours thereafter the solution was evaporated in vacuum and purified using reverse phase HPLC, mobile phase with a gradient 15-80% acetonitrile in 50 min. Fractions containing pure product were evaporated, the residue was dissolved in dichloromethane, which was washed with aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate and evaporated in vacuum to yield 13 mg of the product as the free base off-white Solid. LC-MSD, m/z for C29H34N2O5 [M+H]+: 491.2. 1H NMR (400 MHz, CDCl3): δ 1.2-2.3 (m, 11 H), 1.7 (s, 6 H), 3.2-3.9 (m, 4 H), 3.9 (s, 3 H), 4.7-4.9 (m, 1 H), 4.9-5.0 (m, 1 H), 6.7 (s, 1H), 6.7-6.9 (m, 2H), 7.2-7.3 (m, 2H), 7.4-7.5 (m, 1 H), 7.5-7.6 (m, 1 H).

Workup

  1. custom2 hours thereafter the solution was evaporated in vacuum
  2. custompurified
  3. customin 50 min
  4. additionFractions containing pure product
  5. customwere evaporated
  6. dissolutionthe residue was dissolved in dichloromethane
  7. washwhich was washed with aqueous sodium bicarbonate
  8. dry with materialdried with anhydrous magnesium sulfate
  9. customevaporated in vacuum

Sources & evidence

ORD record
ord-d061a639e7de4777a5e90afc4f49c1b6
Source dataset
uspto-grants-2008_08
Patent number
US07417062B2

Reaction notes

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