1-Tert-butyl-4-hydrazinylpiperidine hydrochloride → 9-(1-(1-tert-butylpiperidin-4-yl)-1H-1,2,4-triazol-5-yl)-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530658Notes

Reaction equation

HRID 1530658 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.[C:32]([N:36]1[CH2:41][CH2:40][CH:39]([NH:42][NH2:43])[CH2:38][CH2:37]1)([CH3:35])([CH3:34])[CH3:33]>CC(O)=O>[C:32]([N:36]1[CH2:37][CH2:38][CH:39]([N:42]2[C:6]([C:8]3[CH:21]=[CH:20][C:19]4[C:18]5[N:14]([CH:15]=[C:16]([C:22]6[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[C:24]([CH3:30])[N:23]=6)[N:17]=5)[CH2:13][CH2:12][O:11][C:10]=4[CH:9]=3)=[N:5][CH:4]=[N:43]2)[CH2:40][CH2:41]1)([CH3:35])([CH3:33])[CH3:34]

Participants

4

Reactant 2

HCID 683129781-Tert-butyl-4-hydrazinylpiperidine hydrochlorideHCID 178432611HCID 178432611, compound

Product 1

HCID 683131679-(1-(1-tert-butylpiperidin-4-yl)-1H-1,2,4-triazol-5-yl)-2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 48.5%

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]tetradeca-1(14),2,4,10,12-pentaene-12-carboxamide (50 mg, 0.12 mmol) and 1-tert-butyl-4-hydrazinylpiperidine hydrochloride (51 mg, 0.25 mmol) in AcOH (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 258 (30 mg, 48% yield) as a white solid. LCMS (ESI): RT=4.77 min, m/z: 516.4 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.58-8.57 (d, J=8.0 Hz, 1H), 8.07 (s, 1H), 7.99 (s, 1H), 7.43-7.41 (dd, J=8.5, 2.0 Hz, 1H), 7.30 (d, J=1.5 Hz, 1H), 5.86 (m, 1H), 4.58 (s, 4H), 4.29 (m, 1H), 3.08-3.06 (m, 2H), 2.26 (s, 3H), 2.13-2.02 (m, 6H), 1.48-1.47 (d, J=6.5 Hz, 6H), 1.02 (s, 9H)

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-bfad5f18d2924b94a8eab083bcab489a
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

Loading…