Trimethylsilylacetylene → 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine

HRID 1628051Notes

Reaction equation

HRID 1628051 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([C:9]#[C:10][C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]([CH3:22])[CH:12]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C([Si](C)(C)C)#C.BrC1C(N)=NC=C(Br)N=1.IC1C2C(=CC=C(OC)C=2)N(C)C=1.CC([O-])(C)C.[K+]>O.CN1C(=O)CCC1>[Br:1][C:2]1[N:3]=[C:4]2[CH:9]=[C:10]([C:11]3[C:19]4[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]([CH3:22])[CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

8

Reactant 5

HCID 66111TrimethylsilylacetyleneHCID 6200042-Amino-3,5-dibromopyrazineHCID 23665647Potassium tert-butoxideHCID 534021023-Iodo-5-methoxy-1-methyl-1H-indoleHCID 580100635-Bromo-3-((5-methoxy-1-methyl-1H-indol-3-yl)ethynyl)pyrazin-2-amine

Product 1

HCID 498306752-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazineYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a round bottom flask was added 5-bromo-3-((5-methoxy-1-methyl-1H-indol-3-yl)ethynyl)pyrazin-2-amine (11.1 g, 30.9 mmol, prepared using General Procedure A from ethynyltrimethylsilane with 3,5-dibromopyrazine-2-amine, Q, A with 3-iodo-5-methoxy-1-methyl-1H-indole (Preparation #11, Step A), NMP (100 mL) and KOt-Bu (6.94 g, 61.9 mmol). The mixture was stirred at rt for about 45 min and then warmed to about 45° C. for about 1.25 h. The mixture was cooled to about 0° C. and then diluted with water (550 mL). The solid was collected by filtration and washed with water (100 mL). The material was dried under vacuum at about 65° C. overnight to give 2-bromo-6-(5-methoxy-1-methyl-1H-indol-3-yl)-5H-pyrrolo[2,3-b]pyrazine (6.61 g; 60%): LC/MS (Table 2, Method a) Rt=2.47 min; MS m/z 357 (M+H)+.

Workup

  1. customprepared
  2. temperaturewarmed to about 45° C. for about 1.25 h
  3. temperatureThe mixture was cooled to about 0° C.
  4. filtrationThe solid was collected by filtration
  5. washwashed with water (100 mL)
  6. customThe material was dried under vacuum at about 65° C. overnight

Sources & evidence

ORD record
ord-bd3ac033886145c49f46282c606b0d8d
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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