Acetamidine → 12-bromo-4-[1-(2-methoxypropyl)-3-methyl-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene

HRID 1530621Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[N:8]([CH:9]=[C:10](I)[N:11]=1)[CH2:7][CH2:6][O:5]2.[C:17](=[NH:20])([NH2:19])[CH3:18].CC1(C)C2[C:43](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:42][C:24]2[C:25](P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:23]1=2.COC(C)[CH2:66][NH:67]N>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:66]3[N:67]([CH2:23][CH:24]([O:42][CH3:43])[CH3:25])[N:19]=[C:17]([CH3:18])[N:20]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of 12-bromo-4-iodo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (1.0 g, 2.6 mmol) in dry DMF (20 mL) was added hydrochloric acetimidamide (266 mg, 2.81 mmol), Pd(OAc)2 (58 mg, 0.26 mmol), and Xantphos (305 mg, 0.520 mmol). The reaction mixture was stirred at 40° C. for 3 h under carbon monoxide atmosphere. LCMS indicated complete conversion. Acetic acid (40 mL) and hydrochloric (2-methoxypropyl)hydrazine (577 mg, 5.20 mmol) were added, the resultant mixture was stirred at 100° C. for 1 h. After concentration, the residue was purified by silica gel chromatography eluting with DCM/methanol (100:1) to give 12-bromo-4-[1-(2-methoxypropyl)-3-methyl-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaene (707 mg, 65% yield) as white solid. LCMS (ESI) m/z: 418.3 [M+H+].

Workup

concentrationAfter concentration
customthe residue was purified by silica gel chromatography
washeluting with DCM/methanol (100:1)

Sources & evidence

ORD record: ord-206ad0d57fff456c975f5a33409fc63a
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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