Thionyl Chloride → (1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine

HRID 1969707Notes

Reaction equation

[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][NH:21][C:22]([C@@H:24]3[CH2:28][CH2:27][C@@H:26]([NH:29]C(=O)OC(C)(C)C)[CH2:25]3)=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].CCN(C(C)C)C(C)C.O=S(Cl)Cl>O1CCOCC1>[S:1]([N:11]1[C:15]2[N:16]=[CH:17][C:18]3[N:19]([C:22]([C@@H:24]4[CH2:28][CH2:27][C@@H:26]([NH2:29])[CH2:25]4)=[N:21][N:20]=3)[C:14]=2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:2])=[O:3]

Participants

Conditions

Temperature: 80 °C

Procedure

To tert-butyl (1R,3R)-3-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinecarbonyl)cyclo-pentylcarbamate (5.03 g, 9.78 mmol) in 1,4-dioxane (103 mL) was added DIEA (7.2 mL, 41 mmol) and SOCl2 (2.3 mL, 31 mmol). The reaction mixture was heated at about 80° C. for about 1 h. The solvent was removed under reduced pressure and the residue was purified using silica gel chromatography (330 g) eluting with a gradient of 0-20% MeOH in DCM to give (1R,3R)-3-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanamine (2.65 g, 68%): LC/MS (Table 1, Method b) Rt=1.55 min; MS m/z: 397 (M+H)+.

Workup

customThe solvent was removed under reduced pressure
customthe residue was purified
washeluting with a gradient of 0-20% MeOH in DCM

Sources & evidence

ORD record: ord-8952182c54984e5ea4d446756fa4aab6
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426411B2

Reaction notes

Loading…