Potassium tert-butoxide → (7S,8aS)-tert-butyl 7-(5-cyclopropylpyrazin-2-yloxy)hexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 240436Notes

Reaction equation

HRID 240436 reaction equation
[OH:1][C@@H:2]1[CH2:17][N:5]2[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C@@H:4]2[CH2:3]1.CC(C)([O-])C.[K+].Br[C:25]1[CH:30]=[N:29][C:28]([CH:31]2[CH2:33][CH2:32]2)=[CH:27][N:26]=1>O1CCCC1>[CH:31]1([C:28]2[N:29]=[CH:30][C:25]([O:1][C@@H:2]3[CH2:17][N:5]4[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:9][C@@H:4]4[CH2:3]3)=[N:26][CH:27]=2)[CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 457876352-Bromo-5-cyclopropylpyrazineHCID 72698247(7S,8aS)-tert-butyl 7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Product 1

HCID 86680448(7S,8aS)-tert-butyl 7-(5-cyclopropylpyrazin-2-yloxy)hexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (7S,8aS)-tert-butyl 7-hydroxyhexahydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate (Wuxi Pharma, 0.485 g, 2 mmol) in tetrahydrofuran (0.3 mL) was added potassium tert-butoxide (2.8 mL, 1 M in tetrahydrofuran, 2.8 mmol) followed by a solution of 2-bromo-5-cyclopropylpyrazine (446 mg, 2.24 mmol) in tetrahydrofuran (1 mL). The mixture was stirred at room temperature for 16 hours. The mixture was concentrated, and the residue was purified by chromatography on silica gel (ethyl acetate) to give the titled compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80 (m, 2H), 0.92 (m, 2H), 1.39 (s, 9H), 1.90 (m, 2H), 2.09 (m, 1H), 2.40 (m, 3H), 2.90 (m, 2H), 3.08 (m, 1H), 3.28 (m, 1H), 3.86-4.08 (m, 2H), 5.27 (m, 1H), 8.11 (m, 2H); MS (ESI) m/z 361 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-16b8b299b1784d15a9c457e7d3af0a19
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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