2-Bromoethanol → 5-(6-(2-hydroxyethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

HRID 45099Notes

Reaction equation

HRID 45099 reaction equation
[N:1]1[C:6]2[CH2:7][NH:8][CH2:9][C:5]=2[C:4]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)=[O:21])[CH:15]=[CH:14]3)=[N:3][CH:2]=1.Br[CH2:34][CH2:35][OH:36]>CN(C=O)C>[OH:36][CH2:35][CH2:34][N:8]1[CH2:9][C:5]2[C:4]([O:10][C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[N:16]([C:20]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:31])([F:30])[F:32])[CH:24]=3)=[O:21])[CH:15]=[CH:14]4)=[N:3][CH:2]=[N:1][C:6]=2[CH2:7]1

Participants

4

Reactant 2

HCID 108982-BromoethanolHCID 593944295-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Product 1

HCID 593942055-(6-(2-hydroxyethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide (125.9 mg, 0.287 mmol) is dissolved in DMF (5 mL) and TEA (80 μL, 0.577 mmol) is added followed by 2-bromoethanol (80 μL, 1.133 mmol). The solution is stirred at rt overnight. Then the reaction is concentrated and absorbed onto silica gel and separated via FCC (0-10%, 10% NH4 in MeOH:DCM) to obtain 5-(6-(2-hydroxyethyl)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide. MS (ESI) m/z 484.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.38 (s, 1 H)8.56 (s, 1 H)8.27 (d, J=9.09 Hz, 1 H)8.09-8.14 (m, 2 H)7.97 (d, J=7.58 Hz, 1 H)7.65 (t, J=8.08 Hz, 1 H)7.48-7.52 (m, 2 H)7.15 (dd, J=8.84, 2.53 Hz, 1 H)6.80 (d, J=3.54 Hz, 1 H)4.57 (t, J=5.56 Hz, 1 H)3.98-4.03 (m, 4 H)3.58 (q, J=6.06 Hz, 2 H) 2.82 (t, J=6.06 Hz, 2 H).

Workup

  1. concentrationThen the reaction is concentrated
  2. customabsorbed onto silica gel
  3. customseparated via FCC (0-10%, 10% NH4 in MeOH:DCM)

Sources & evidence

ORD record
ord-27fca19cd601442e8d112d74bbc4c0a9
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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