Triethylamine → (7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-4(1H)-one

HRID 1184609Notes

Reaction equation

HRID 1184609 reaction equation
Cl.[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:16][NH:15][C@H:14]([CH2:17][NH:18][CH2:19][C:20]([O:22]C)=O)[CH2:13]3)=[N:9][CH:10]=2)[CH2:4][CH2:3]1.C(N(CC)CC)C>CO>[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([O:11][C@H:12]3[CH2:16][N:15]4[C:20](=[O:22])[CH2:19][NH:18][CH2:17][C@@H:14]4[CH2:13]3)=[N:9][CH:10]=2)[CH2:3][CH2:4]1

Participants

4

Reactant 2

HCID 8471TriethylamineHCID 86680522methyl 2-((((2S,4R)-4-((5-cyclopropylpyrazin-2-yl)oxy)pyrrolidin-2-yl)-methyl)amino)acetate hydrochloride

Product 1

HCID 86680524(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]hexahydropyrrolo[1,2-a]-pyrazin-4(1H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product from Example 174F (0.958 g, 2.79 mmol) in methanol (10 mL) was added triethylamine (2.337 mL, 16.77 mmol). The mixture was heated to reflux and stirred for 18 hours. The cooled mixture was concentrated in vacuo, and the crude product was purified by flash chromatography on a 12 g silica gel column, eluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes and then a gradient to 10% methanol (2 N ammonia) in dichloromethane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.15 (dd, J=9.2, 1.4 Hz, 2H), 5.47 (t, J=5.0 Hz, 1H), 4.05-3.88 (m, 1H), 3.87-3.69 (m, 1H), 3.26-3.01 (m, 4H), 2.67 (s, 1H), 2.34 (dd, J=12.7, 10.2 Hz, 1H), 2.24-2.03 (m, 2H), 1.73 (ddd, J=13.3, 11.9, 4.8 Hz, 1H), 1.03-0.88 (m, 2H), 0.82 (ddd, J=6.8, 4.7, 2.4 Hz, 2H); MS (ESI) m/z 449 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. concentrationThe cooled mixture was concentrated in vacuo
  4. customthe crude product was purified by flash chromatography on a 12 g silica gel column
  5. washeluting with 2.5% methanol (containing 2 N ammonia) in dichloromethane for 3 minutes

Sources & evidence

ORD record
ord-2e6146319f014eeaa6783e14390171f7
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

Loading…