Water → HCID 86680516, compound

HRID 1184598Notes

Reaction equation

HRID 1184598 reaction equation
[OH:1][C@H:2]1[CH2:11][N:5]2[CH2:6][CH2:7][NH:8][C:9](=[O:10])[C@@H:4]2[CH2:3]1.CC(C)([O-])C.[Na+].Br[C:19]1[CH:24]=[N:23][C:22]([CH:25]2[CH2:27][CH2:26]2)=[CH:21][N:20]=1.O>CS(C)=O>[CH:25]1([C:22]2[N:23]=[CH:24][C:19]([O:1][CH:2]3[CH2:11][N:5]4[CH2:6][CH2:7][NH:8][C:9](=[O:10])[CH:4]4[CH2:3]3)=[N:20][CH:21]=2)[CH2:27][CH2:26]1

Participants

6

Reactant 4

HCID 962WaterHCID 23676156Sodium t-butoxideHCID 45099453HCID 45099453, compoundHCID 457876352-Bromo-5-cyclopropylpyrazine

Product 1

HCID 86680516HCID 86680516, compoundYield 23.72%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

In a 4 mL vial were combined (7R,8aS)-7-hydroxyhexahydro-pyrrolo[1,2-a]pyrazin-1(2H)-one (180 mg, 1.152 mmol) from Step 2 and sodium tert-butoxide (188 mg, 1.959 mmol) in dimethyl sulfoxide (1 mL). The mixture was stirred at room temperature for 0.4 hours followed by the addition of 2-bromo-5-cyclopropyl-pyrazine (229 mg, 1.152 mmol). After stirring at room temperature for 8 hours, water was added, and the solution was extracted with ethyl acetate. The extract was concentrated in vacuo, and the resulting solid was purified using an Agilent Technologies SuperFlash SF-15-12 g cartridge eluted with a gradient of 0-8% methanol/dichloromethane over 20 minutes to give 7-(5-cyclopropylpyrazin-2-yloxy)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one (75 mg, 0.273 mmol, 23.72% yield) as an oil in a 3:1 (7R,8aS: 7R,8aR) diastereomer ratio. 1H NMR (500 MHz, pyridine-d5) δ ppm 8.44 (d, J=32.4 Hz, 1H), 8.19 (dd, J=14.4, 0.9 Hz, 1H), 8.12-8.05 (m, 1H), 5.54-5.41 (m, 1H), 3.77 (t, J=8.0 Hz, 0.5H), 3.54 (dddd, J=12.4, 10.1, 8.1, 4.0 Hz, 1H), 3.49-3.35 (m, 1H), 3.30-3.19 (m, 1.5H), 3.02 (ddd, J=16.9, 9.2, 4.7 Hz, 1H), 2.91 (dt, J=7.7, 4.2 Hz, 1H), 2.89-2.80 (m, 1H), 2.80-2.66 (m, 1H), 2.60-2.51 (m, 1H), 2.00 (qt, J=9.5, 4.8 Hz, 1H), 1.12-1.02 (m, 2H), 0.96-0.86 (m, 2H); MS (ESI+) m/z 275 (M+H)+.

Workup

  1. stirringAfter stirring at room temperature for 8 hours
  2. extractionthe solution was extracted with ethyl acetate
  3. concentrationThe extract was concentrated in vacuo
  4. customthe resulting solid was purified
  5. washeluted with a gradient of 0-8% methanol/dichloromethane over 20 minutes

Sources & evidence

ORD record
ord-d268162082b34ae99c03aa70fba6fd13
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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