Potassium tert-butoxide → (8S,9aS)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

HRID 572036Notes

Reaction equation

HRID 572036 reaction equation
[OH:1][C@@H:2]1[CH2:22][N:5]2[C:6](=[O:21])[CH2:7][CH2:8][N:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]=3)[CH2:10][C@@H:4]2[CH2:3]1.Br[C:24]1[CH:29]=[N:28][C:27]([CH:30]2[CH2:32][CH2:31]2)=[CH:26][N:25]=1.CC(C)([O-])C.[K+]>O1CCCC1>[CH:30]1([C:27]2[N:28]=[CH:29][C:24]([O:1][C@@H:2]3[CH2:22][N:5]4[C:6](=[O:21])[CH2:7][CH2:8][N:9]([C:11]5[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][N:12]=5)[CH2:10][C@@H:4]4[CH2:3]3)=[N:25][CH:26]=2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 457876352-Bromo-5-cyclopropylpyrazineHCID 86723184(8S,9aS)-8-hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one

Product 1

HCID 76285914(8S,9aS)-8-[(5-cyclopropylpyrazin-2-yl)oxy]-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-oneYield 47.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To (8S,9aS)-8-hydroxy-2-[5-(trifluoromethyl)pyridin-2-yl]octahydro-5H-pyrrolo[1,2-a][1,4]diazepin-5-one (74 mg, 0.235 mmol, Part D), 2-bromo-5-cyclopropylpyrazine (79 mg, 0.4 mmol) in tetrahydrofuran (1.2 mL) was added potassium tert-butoxide (0.47 ml, 0.47 mmol, 1 M in tetrahydrofuran). The mixture was stirred at room temperature overnight. The mixture was purified by chromatography on silica gel (ethyl acetate) to give 48 mg (47%) of the titled compound as a solid. 1H NMR (400 MHz, CDCl3) δ ppm 0.88-1.04 (m, 4H), 2.00 (m, 1 H), 2.15 (br d, J=14 Hz, 1 H), 2.66 (m, 1 H), 2.72 (m, 2 H), 3.36 (dd, J=14, 10 Hz, 1 H), 3.48 (m, 1 H), 3.83 (dd, J=12, 8 Hz, 1 H), 3.90 (br d, J=12 Hz, 1 H), 4.03 (m, 1H), 4.34 (br d, J=15 Hz, 1 H), 4.63 (d, J=14 Hz, 1 H), 5.44 (m, 1H), 6.65 (d, J=9 Hz, 1 H), 7.66 (dd, J=9, 2 Hz, 1 H), 7.95 (s, 1 H), 8.06 (s, 1 H), 8.41 (s, 1 H); MS (ESI) m/z 434.0 (M+H)+.

Workup

  1. customThe mixture was purified by chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-2459d18f37a84420ab8074bb36cc882b
Source dataset
uspto-grants-2015_05
Patent number
US09029361B2

Reaction notes

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