Isobutyryl chloride → (S)-5-[3-(5-isopropyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one

HRID 1672796Notes

Reaction equation

[OH:1][N:2]=[C:3]([NH2:27])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[CH2:19][C@H:18]3[N:14]([CH2:15][CH2:16][CH2:17]3)[C:13]3[N:20]=[C:21]([S:24][CH3:25])[N:22]=[CH:23][C:12]=3[C:11]2=[O:26])[CH:5]=1.[CH:28]([C:31](Cl)=O)([CH3:30])[CH3:29]>N1C=CC=CC=1.C(Cl)(Cl)Cl>[CH:28]([C:31]1[O:1][N:2]=[C:3]([C:4]2[CH:5]=[C:6]([N:10]3[CH2:19][C@H:18]4[N:14]([CH2:15][CH2:16][CH2:17]4)[C:13]4[N:20]=[C:21]([S:24][CH3:25])[N:22]=[CH:23][C:12]=4[C:11]3=[O:26])[CH:7]=[CH:8][CH:9]=2)[N:27]=1)([CH3:30])[CH3:29]

Participants

Conditions

Temperature: 90 °C

Procedure

(S)—N′-Hydroxy-3-(9-methylthio-6-oxo-2,3,3a,4-tetrahydro-1H,6H-5,8,10,10b-tetraazabenzo[e]azulen-5-yl)benzamidine (120 mg, 0.31 mmol) obtained in Step 1 was dissolved in pyridine (1.5 mL), and the mixture was stirred overnight at 90° C. after adding isopropylcarbonyl chloride (0.039 mL, 0.38 mmol) under ice-cooled conditions. The mixture was diluted with chloroform, washed with water and saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. The residue obtained by concentrating the mixture under reduced pressure was then purified by silica gel column chromatography to give (S)-5-[3-(5-isopropyl-1,2,4-oxadiazol-3-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (149 mg, quantitative).

Workup

temperaturecooled conditions
washwashed with water and saturated brine
dry with materialthe organic layer was dried over anhydrous magnesium sulfate
customThe residue obtained
concentrationby concentrating the mixture under reduced pressure
customwas then purified by silica gel column chromatography

Sources & evidence

ORD record: ord-b84332486d154766ba3dc412fa439b19
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998954B2

Reaction notes

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