Water → ethyl 2-methyl-2-[3-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)piperidin-1-yl]propanoate

HRID 1530636Notes

Reaction equation

HRID 1530636 reaction equation
[CH3:1][C:2]1[N:6]=[C:5]([C:7]2[N:8]=[C:9]3[N:19]([CH:20]=2)[CH2:18][CH2:17][O:16][C:15]2[C:10]3=[CH:11][CH:12]=[C:13]([C:21]3[CH:22]=[N:23][N:24]([CH3:32])[C:25]=3[CH:26]3[CH2:31][CH2:30][CH2:29][NH:28][CH2:27]3)[CH:14]=2)[N:4]([CH:33]([CH3:35])[CH3:34])[N:3]=1.Br[C:37]([CH3:44])([CH3:43])[C:38]([O:40][CH2:41][CH3:42])=[O:39].O>CC#N>[CH3:43][C:37]([N:28]1[CH2:29][CH2:30][CH2:31][CH:26]([C:25]2[N:24]([CH3:32])[N:23]=[CH:22][C:21]=2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[C:9]2[N:19]([CH:20]=[C:7]([C:5]4[N:4]([CH:33]([CH3:35])[CH3:34])[N:3]=[C:2]([CH3:1])[N:6]=4)[N:8]=2)[CH2:18][CH2:17][O:16]3)[CH2:27]1)([CH3:44])[C:38]([O:40][CH2:41][CH3:42])=[O:39]

Participants

5

Reactant 3

HCID 962WaterHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 683127572-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

Product 1

HCID 68312948ethyl 2-methyl-2-[3-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)piperidin-1-yl]propanoateYield 47%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-12-[1-methyl-5-(piperidin-3-yl)-1H-pyrazol-4-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1 (14),2,4,10,12-pentaene (60 mg, 0.127 mmol), ethyl 2-bromo-2-methylpropanoate (247.65 mg, 1.27 mmol), Ag2O (294 mg, 1.27 mmol), H2O (0.1 ml) and CH3CN (1.5 ml) in a seal tube was heated at 60° C. for 8 h. The solid was filtered off and the filtrate was purified by Combiflash eluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3 to afford ethyl 2-methyl-2-[3-(1-methyl-4-{4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca1(14),2,4,10,12-pentaen-12-yl}-1H-pyrazol-5-yl)piperidin-1-yl]propanoate (35 mg, 47% yield). LCMS (ESI) m/z: 589.3 [M+H+]

Workup

  1. filtrationThe solid was filtered off
  2. customthe filtrate was purified by Combiflash
  3. washeluting with a 0-70% gradient of CH3CN in 0.3% NH4HCO3

Sources & evidence

ORD record
ord-0f6d203769a3455fb8dcaacc22834a96
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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