4-Hydrazinyl-1-methylpiperidine hydrochloride → 2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-(1-methylpiperidin-4-yl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530651Notes

Reaction equation

HRID 1530651 reaction equation
CN(/[CH:4]=[N:5]/[C:6]([C:8]1[CH:9]=[C:10]2[C:19](=[CH:20][CH:21]=1)[C:18]1[N:14]([CH:15]=[C:16]([C:22]3[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[C:24]([CH3:30])[N:23]=3)[N:17]=1)[CH2:13][CH2:12][O:11]2)=O)C.Cl.[NH:32]([CH:34]1[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]1)[NH2:33]>C(O)(=O)C>[CH:27]([N:26]1[C:22]([C:16]2[N:17]=[C:18]3[C:19]4[CH:20]=[CH:21][C:8]([C:6]5[N:32]([CH:34]6[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]6)[N:33]=[CH:4][N:5]=5)=[CH:9][C:10]=4[O:11][CH2:12][CH2:13][N:14]3[CH:15]=2)=[N:23][C:24]([CH3:30])=[N:25]1)([CH3:28])[CH3:29]

Participants

4

Reactant 2

HCID 683128814-Hydrazinyl-1-methylpiperidine hydrochlorideHCID 178432611HCID 178432611, compound

Product 1

HCID 683131492-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-9-(1-(1-methylpiperidin-4-yl)-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 34.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-[(1E)-(dimethylamino)methylidene]-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-pentaene-12-carboxamide (100 mg, 0.246 mmol) and 4-hydrazinyl-1-methylpiperidine hydrochloride (81 mg, 0.49 mmol) in acetic acid (10 mL) was heated at 100° C. for 1 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 255 (40 mg, 34% yield) as a white solid. LCMS (ESI): RT=4.28 min, m/z: 474.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.58-8.57 (d, J=8.0 Hz, 1H), 8.08 (s, 1H), 7.99 (s, 1H), 7.44-7.42 (dd, J=8.0, 1.5 Hz, 1H), 7.31 (d, J=1.5 Hz, 1H), 5.86 (m, 1H), 4.58 (s, 4H), 4.31 (m, 1H), 2.86-2.84 (m, 2H), 2.26 (s, 3H), 2.18 (s, 3H), 2.13-2.07 (m, 2H), 2.01-1.96 (m, 2H), 1.91-1.89 (m, 2H), 1.47 (d, J=6.5 Hz, 6H)

Workup

  1. customThe solvent was removed
  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-284ea762226a4699ae9aa5b1048b04b7
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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