Acetamidine monohydrochloride → 2-(5-{12-bromo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-4-yl}-3-methyl-1H-1,2,4-triazol-1-yl)ethan-1-ol

HRID 1530624Notes

Reaction equation

HRID 1530624 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.Cl.[C:18](=[NH:21])([NH2:20])[CH3:19].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:43][C:25]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=C[C:24]1=2.Cl.[NH:65]([CH2:67]CO)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:67]3[N:65]([CH2:24][CH2:25][OH:43])[N:20]=[C:18]([CH3:19])[N:21]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2

Participants

8

Reactant 4

HCID 67170Acetamidine monohydrochlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582048589-Bromo-2-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepineHCID 866714732-Hydrazinylethanol hydrochloride

Product 1

HCID 683128562-(5-{12-bromo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-4-yl}-3-methyl-1H-1,2,4-triazol-1-yl)ethan-1-olYield 800.8%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 12-bromo-4-iodo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (100 mg, 0.256 mmol), acetimidamide hydrochloride (26.5 mg, 0.282 mmol), Pd(OAc)2 (2.9 mg, 0.0129 mmol), Xantphos (14.8 mg, 0.0256 mmol), and TEA (77.6 mg, 0.768 mmol) in DMF (5 mL) was heated at 40° C. under CO (1 atm) for 2 h. After cooling to room temperature, 2-hydrazinylethanol hydrochloride (57.3 mg, 0.512 mmol) and acetic acid (5 mL) were added. The resulting mixture was heated at 80° C. for 0.5 h. The solvent was removed under reduce pressure and the residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 2-(5-{12-bromo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaen-4-yl}-3-methyl-1H-1,2,4-triazol-1-yl)ethan-1-ol (80 mg, 80% yield) as white solid. LCMS (ESI) m/z: 390.1 [M+H+].

Workup

  1. temperatureAfter cooling to room temperature
  2. temperatureThe resulting mixture was heated at 80° C. for 0.5 h
  3. customThe solvent was removed
  4. customthe residue was purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

Sources & evidence

ORD record
ord-c0c6993013984645a4f42a45fad29e40
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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