1-Benzylpyrrolidin-3-yl methanesulfonate → (S)-6-(1-Benzylpyrrolidin-3-yloxy)-isoquinolin-1-ylamine

HRID 1435960Notes

Reaction equation

HRID 1435960 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([OH:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(P1(N(C)CCCN1)=NC(C)(C)C)CC.[CH2:30]([N:37]1[CH2:41][CH2:40][CH:39](OS(C)(=O)=O)[CH2:38]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(#N)C>[CH2:30]([N:37]1[CH2:41][CH2:40][C@H:39]([O:12][C:8]2[CH:7]=[C:6]3[C:11](=[CH:10][CH:9]=2)[C:2]([NH2:1])=[N:3][CH:4]=[CH:5]3)[CH2:38]1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 98998111-Benzylpyrrolidin-3-yl methanesulfonateHCID 199900182-tert-butylimino-N,N-diethyl-1-methyl-1,3,2lambda5-diazaphosphinan-2-amineHCID 1357539911-Aminoisoquinolin-6-ol

Product 1

HCID 68874970(S)-6-(1-Benzylpyrrolidin-3-yloxy)-isoquinolin-1-ylamineYield 40.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

1-Amino-6-hydroxyisoquinoline (50 mg, 0.312 mmol), prepared as described in WO 00/24718 (Akzo Nobel N.V.), and 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (284 mg, ˜2.2 mmol.g−1, ˜0.624 mmol) were stirred at ambient temperature in acetonitrile (4 ml) for 15 min. (R) Methanesulfonic acid 1-benzylpyrrolidin-3yl ester (0.312 mmol) was added and the mixture heated to 110° C. and stirred for 60 h. The mixture was filtered and the precipitate washed with acetonitrile. The filtrate was concentrated and then purified by prep-HPLC to give (S)-6-(1-Benzylpyrrolidin-3-yloxy)-isoquinolin-1-ylamine (40 mg),

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered
  3. washthe precipitate washed with acetonitrile
  4. concentrationThe filtrate was concentrated
  5. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-f1eb9e119b2b4a98a2767c23c61efedf
Source dataset
uspto-grants-2009_11
Patent number
US07618985B2

Reaction notes

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