Bromine → 7-Benzyl-1-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine

HRID 515775Notes

Reaction equation

HRID 515775 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[C:14](Br)=[N:15][CH:16]=[C:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1CCN2C=NC=C2C1)C1C=CC=CC=1.C([Li])CCC.[Br:39]Br>C1COCC1.O>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]2[CH:14]=[N:15][C:16]([Br:39])=[C:10]2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24408BromineHCID 223352507-Benzyl-3-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine2×HCID 223353867-Benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazineHCID 178418339Butyllithium

Product 1

HCID 716072067-Benzyl-1-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazineYield 18.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

7-Benzyl-3-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine: The synthesis of 7-benzyl-3-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine is described in PCT/IB03/00998 WO 03/076427 A1. A solution of 7-benzyl-5,6,7,8-tetrahydro imidazo[1,5-a]pyrazine (450 mg, 2.110 mmol) in THF was cooled in dry ice acetone bath. n-Butyllithium (0.928 mL, 2.321 mmol) was added dropwise. After 15 mins, bromine (0.120 mL, 2.321 mmol) was added dropwise. After 1 h, the solution was poured into H2O and extracted with DCM (3×). Purified by normal phase chromatography to afford 7-benzyl-1-bromo-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine (112 mg, 0.383 mmol, 18.2% yield) and 71A (260 mg, 0.890 mmol, 42.2% yield). 1H NMR (400 MHz, CDCl3) δ 7.18-7.44 (m, 5 H) 6.71 (s, 1 H) 3.78-3.95 (m, 2 H) 3.68 (s, 2 H) 3.60 (s, 2 H) 2.75-2.97 (m, 2 H) ppm.

Workup

  1. waitAfter 1 h
  2. extractionextracted with DCM (3×)
  3. customPurified by normal phase chromatography

Sources & evidence

ORD record
ord-64f449f16d7349a7bae91d4be306d6eb
Source dataset
uspto-grants-2015_08
Patent number
US09108951B2

Reaction notes

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