Diisopropylethylamine → 2-(bromomethyl)-N-(2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl)benzamide

HRID 627788Notes

Reaction equation

HRID 627788 reaction equation
[Br:1][C:2]1[N:3]=[C:4]2[C:10]([NH2:11])=[CH:9][N:8]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:5]2=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[Br:40][CH2:41][C:42]1[CH:50]=[CH:49][CH:48]=[CH:47][C:43]=1[C:44](Cl)=[O:45]>C1COCC1>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([NH:11][C:44](=[O:45])[C:43]3[CH:47]=[CH:48][CH:49]=[CH:50][C:42]=3[CH2:41][Br:40])=[CH:9][N:8]([C:12]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122516322-Bromomethylbenzoyl chlorideHCID 866757072-Bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine

Product 1

HCID 866765052-(bromomethyl)-N-(2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl)benzamideYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine (3 g, 6.588 mmol) dissolved in THF (30 mL) under N2 at rt. DIPEA (5.7 mL, 32.9 mmol) added followed by a solution of 2-(bromomethyl)benzoyl chloride (1.9 g, 8.137 mmol) in THF (10 mL). Reaction mixture stirred overnight then partitioned between EtOAc and water. Aqueous phase extracted with EtOAc. Combined organics washed with saturated NaHCO3 solution then brine, dried and concentrated. Residue taken up in DCM and purified by chromatography (0-40% EtOAc-petroleum ether gradient). Further purification by chromatography (isocratic DCM elution) gives the title compound as a yellow foam (1.45 g, 34%); 1H NMR (400 MHz, DMSO) δ 4.93 (2H, s), 7.21-7.38 (15H, m), 7.44-7.61 (3H, m), 7.62 (1H, d), 8.19 (1H, s), 8.59 (1H, s), 10.93 (1H, s) ppm; MS (ES+) 653.0.

Workup

  1. customReaction mixture
  2. customthen partitioned between EtOAc and water
  3. extractionAqueous phase extracted with EtOAc
  4. washCombined organics washed with saturated NaHCO3 solution
  5. dry with materialbrine, dried
  6. concentrationconcentrated
  7. custompurified by chromatography (0-40% EtOAc-petroleum ether gradient)
  8. customFurther purification
  9. washby chromatography (isocratic DCM elution)

Sources & evidence

ORD record
ord-05107cd01ec54c4eb77522e3a791a6ad
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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