2-Bromoacetamide → 5-(6-carbamoylmethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 45101

Reaktionsgleichung

Reaktionsgleichung von HRID 45101
[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][C:35]([NH2:37])=[O:36]>CN(C=O)C>[F:32][C:29]([F:31])([F:30])[C:25]1[CH:24]=[C:23]([NH:22][C:20]([N:16]2[C:17]3[C:13](=[CH:12][C:11]([O:10][C:4]4[C:5]5[CH2:9][N:8]([CH2:34][C:35](=[O:36])[NH2:37])[CH2:7][C:6]=5[N:1]=[CH:2][N:3]=4)=[CH:19][CH:18]=3)[CH:14]=[CH:15]2)=[O:21])[CH:28]=[CH:27][CH:26]=1

Komponenten

4

Edukt 2

HCID 696322-BromoacetamideHCID 593944295-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide

Produkt 1

HCID 593947095-(6-carbamoylmethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-N-(3-(trifluoromethyl)phenyl)-1H-indole-1-carboxamide (217 mg, 0.494 mmol) is dissolved in DMF (5 mL) and TEA (160 μl, 1.15 mmol) is added followed by 2-bromoacetamide (250 mg, 1.81 mmol). The solution is stirred at it for 1 h. The reaction is concentrated and the residue absorbed onto silica gel and separated via FCC (0-10%, 10% NH4 in MeOH:DCM) to obtain 5-(6-carbamoylmethyl-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 497.9 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 10.38 (br. S., 1 H)8.58 (s, 1 H)8.27 (d, J=8.84 Hz, 1 H)8.09-8.13 (m, 2 H)7.96 (s, 1 H)7.65 (t, J=8.08 Hz, 1 H)7.48-7.51 (m, 2 H)7.38 (br. S., 1 H)7.09-7.17 (m, 2 H) 6.80 (d, J=3.03 Hz, 1 H)4.12 (dd, J=10.61, 2.02 Hz, 4H)3.38 (s, 2 H).

Aufarbeitung

  1. concentrationThe reaction is concentrated
  2. customthe residue absorbed onto silica gel
  3. customseparated via FCC (0-10%, 10% NH4 in MeOH:DCM)

Quellen und Nachweise

ORD-Eintrag
ord-9489ac5b1d7c43d2bd8baf428adc0a3a
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541432B2

Verknüpfte Notizen

Wird geladen…