Ethanol → 2-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)-thiazole-5-carbonitrile

HRID 1969763Notes

Reaction equation

[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][N:17](S(C5C=CC(C)=CC=5)(=O)=O)[C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][C:31]2[S:32][C:33]([C:36]#[N:37])=[CH:34][N:35]=2)[CH2:4]1)[CH3:2].O1CCOCC1.CCO.C([O-])([O-])=O.[Na+].[Na+]>CC(O)=O>[CH2:1]([C@H:3]1[C@@H:7]([C:8]2[N:12]3[C:13]4[CH:19]=[CH:18][NH:17][C:14]=4[N:15]=[CH:16][C:11]3=[N:10][N:9]=2)[CH2:6][C@@H:5]([NH:30][C:31]2[S:32][C:33]([C:36]#[N:37])=[CH:34][N:35]=2)[CH2:4]1)[CH3:2]

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 2-((1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)thiazole-5-carbonitrile (0.21 g, 0.39 mmol), 1,4-dioxane (4.5 mL), EtOH (3.5 mL) and Na2CO3 (2 N aqueous, 5.8 mL, 15.7 mmol) was heated at about 50° C. for about 12 h. The reaction mixture was neutralized to pH 7 by the addition of AcOH (0.3 mL), washed with water (2×5 mL) and extracted with DCM (3×5 mL). The organic layer was dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-5% MeOH in DCM to give 2-((1S,3R,4S)-3-ethyl-4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentylamino)-thiazole-5-carbonitrile (0.09 g, 60%): LC/MS (Table 1, Method c) Rt=1.95 min; MS m/z: 379 (M+H)+.

Workup

washwashed with water (2×5 mL)
extractionextracted with DCM (3×5 mL)
dry with materialThe organic layer was dried over anhydrous MgSO4
filtrationfiltered
customThe crude material was purified by silica gel chromatography
washeluting with a gradient of 0-5% MeOH in DCM

Sources & evidence

ORD record: ord-fb22406a32a24a0ba14e4d0bc4417b6b
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08426411B2

Reaction notes

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