Trifluoroacetic acid → 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid isoquinolin-3-ylmethyl-(S)-1-pyrrolidin-2-ylmethyl-amide

HRID 2220718Notes

Reaction equation

HRID 2220718 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][NH:14][CH2:15][C:16]1[N:17]=[CH:18][C:19]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][CH:20]=2)=O)(C)(C)C.C(N(CC)CC)C.[CH3:33][O:34][C:35]1[C:40]2[O:41][C:42]([CH3:45])([CH3:44])[O:43][C:39]=2[CH:38]=[C:37]([C:46](Cl)=[O:47])[CH:36]=1.FC(F)(F)C(O)=O>ClCCl>[CH:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:25]=[C:16]([CH2:15][N:14]([CH2:13][C@@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)[C:46]([C:37]2[CH:36]=[C:35]([O:34][CH3:33])[C:40]3[O:41][C:42]([CH3:45])([CH3:44])[O:43][C:39]=3[CH:38]=2)=[O:47])[N:17]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 58622151(S)-2-{[(Isoquinolin-3-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 714100777-Methoxy-2,2-dimethyl-2H-1,3-benzodioxole-5-carbonyl chloride

Product 1

HCID 586221577-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid isoquinolin-3-ylmethyl-(S)-1-pyrrolidin-2-ylmethyl-amideYield 43.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Experimental conditions analogous to Example 60, from 0.17 g (0.38 mmol) of (S)-2-{[(isoquinolin-3-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (double trifluoroacetic acid salt), 6 mL dichloromethane, 159 μL (1.14 mmol) of triethylamine, 0.10 g (0.42 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride and 0.6 mL trifluoroacetic acid. Purification using reverse phase HPLC, mobile phase with a gradient 10-70% acetonitrile in 40 min, gave 74 mg of the product as the free base as a colorless solid. LC-MSD, m/z for C26H29N3O4 [M+H]+: 448.6.

Workup

  1. customPurification
  2. customin 40 min

Sources & evidence

ORD record
ord-2e09b3f623364155b55552883fe209c2
Source dataset
uspto-grants-2008_08
Patent number
US07417062B2

Reaction notes

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