Tetrahydro-4H-pyran-4-one → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-methyl-5-(1-(oxetan-3-yl)piperidin-3-yl)-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530607Notes

Reaction equation

HRID 1530607 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.O1[CH2:41][CH2:40][C:39](=[O:42])CC1>CCO>[CH:33]([N:4]1[C:5]([C:7]2[N:8]=[C:9]3[C:10]4[CH:11]=[CH:12][C:13]([C:21]5[CH:22]=[N:23][N:24]([CH3:32])[C:25]=5[CH:26]5[CH2:31][CH2:30][CH2:29][N:28]([CH:40]6[CH2:39][O:42][CH2:41]6)[CH2:27]5)=[CH:14][C:15]=4[O:16][CH2:17][CH2:18][N:19]3[CH:20]=2)=[N:6][C:2]([CH3:1])=[N:3]1)([CH3:35])[CH3:34]

Participants

4

Reactant 2

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 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 665585102-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-methyl-5-(1-(oxetan-3-yl)piperidin-3-yl)-1H-pyrazol-4-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 18%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

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 (80 mg, 0.17 mmol), tetrahydropyran-4-one (25 mg, 0.25 mmol) and Ti(O-iPr)4 (2 drops) in EtOH (20 mL) was stirred at room temperature for 18 h. After concentration, 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 give 213 (16 mg, 18% yield). LCMS (ESI): RT=4.75 min, m/z: 527.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.42 (d, J=8.0 Hz, 1H), 7.91 (s, 1H), 7.43 (s, 1H), 7.08 (d, J=1.5 Hz, 1H), 6.94 (s, 1H), 7.39-7.36 (m, 1H), 5.87-5.84 (m, 1H), 4.54-4.40 (m, 8H), 3.90 (s, 3H), 3.18 (s, 1H), 2.74-2.69 (m, 2H), 2.24 (s, 3H), 2.11-2.06 (m, 1H), 1.78-1.71 (m, 5H), 1.47 (d, J=2.0 Hz, 6H)

Workup

  1. concentrationAfter concentration
  2. 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-de16078085244823993c78228cce28b1
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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