1,1'-Carbonyldiimidazole → (1S,2R)-4'-(4-chlorophenyl)-2,2',3'-trimethylspiro[cyclopropane-1,6'-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-9'(8'H)-one

HRID 1772363Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:22]([CH3:23])=[C:21]([CH3:24])[S:20][C:10]=3[NH:11][C:12](=[N:18][NH2:19])[C@@:13]3([CH2:16][C@H:15]3[CH3:17])[N:14]=2)=[CH:4][CH:3]=1.C1N=CN([C:30](N2C=NC=C2)=[O:31])C=1>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:22]([CH3:23])=[C:21]([CH3:24])[S:20][C:10]=3[N:11]3[C:30](=[O:31])[NH:19][N:18]=[C:12]3[C@@:13]3([CH2:16][C@H:15]3[CH3:17])[N:14]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A disposable tube was charged with (1S,2R)-5′-(4-chlorophenyl)-2′-hydrazono-2,6′,7′-trimethyl-1′,2′-dihydrospiro[cyclopropane-1,3′-thieno[2,3-e][1,4]diazepine] (24 mg, 0.067 mmol) and a stir bar. THF (1.5 mL, 0.05 M) was added, followed by CDI (13.01 mg, 0.080 mmol), and the solution was stirred 85° C. 4 h. At 4 h, more CDI (26 mg, 0.160 mmol) was added, and the reaction was stirred at 85° C. The reaction was concentrated and purified by reverse phase chromatography (water/acetonitrile with 0.1% TFA) to give (1S,2R)-4′-(4-chlorophenyl)-2,2′,3′-trimethylspiro[cyclopropane-1,6′-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin]-9′(8′H)-one (2,2,2-trifluoroacetic acid salt) (Compound 222) as a yellow amorphous solid (17 mg). LRMS (M+H)+: 385 m/z. 1H NMR (400 MHz, DMSO-d6) δ 12.08 (s, 1H), 7.49 (d, J=8.90 Hz, 2H), 7.42 (d, J=8.70 Hz, 2H), 2.34 (s, 3H), 1.52 (s, 3H), 1.18 (s, OH), 1.16 (s, 1H), 1.15 (s, 1H), 0.87 (br. s., 2H).

Workup

custom4 h
stirringthe reaction was stirred at 85° C
concentrationThe reaction was concentrated
custompurified by reverse phase chromatography (water/acetonitrile with 0.1% TFA)

Sources & evidence

ORD record: ord-c54382f91612456bb8a219a52caebcff
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249161B2

Reaction notes

Loading…