Water → (S)-4-chloro-5-[3-(2-hydroxymethylpyrrolidin-1-yl)propoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone

HRID 21330

Reaction equation

HRID 21330 reaction equation
[Cl:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][CH2:14]Cl)=[CH:9][C:8]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:20][CH:19]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:39].[NH:40]1[CH2:44][CH2:43][CH2:42][C@H:41]1[CH2:45][OH:46].O>CN(C)C(=O)C>[Cl:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][CH2:14][N:40]2[CH2:44][CH2:43][CH2:42][C@H:41]2[CH2:45][OH:46])=[CH:9][C:8]([C:16]2[N:17]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:18]3[C:23]([CH:24]=2)=[CH:22][C:21]([CH2:25][N:26]2[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]2)=[CH:20][CH:19]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:39]

Participants

5

Reactant 3

HCID 962WaterHCID 640091L-ProlinolHCID 684918464-Chloro-5-(3-chloropropoxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone

Product 1

HCID 68492874(S)-4-chloro-5-[3-(2-hydroxymethylpyrrolidin-1-yl)propoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinoneYield 69%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

In a similar manner to Step 2 of Example 440, 4-chloro-5-(3-chloropropoxy)-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (119 mg, 0.208 mmol) was dissolved in N,N-dimethylacetoamide (1.2 mL), and the solution was treated with (S)-(+)-2-pyrrolidinemethanol (0.205 mL, 2.08 mmol). The reaction mixture was added with water. The obtained solid was collected by filtration and washed with water, followed by drying under reduced pressure to obtain (S)-4-chloro-5-[3-(2-hydroxymethylpyrrolidin-1-yl)propoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidin-1-ylmethyl)indol-2-yl]isoindolinone (91.0 mg, yield 69%).

Workup

  1. filtrationThe obtained solid was collected by filtration
  2. washwashed with water
  3. customby drying under reduced pressure

Sources & evidence

ORD record
ord-00dbab4037bd455497a26c1f27521292
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Linked notes

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