4-Hydrazinyl-1-methylpiperidine hydrochloride → 2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-methyl-9-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine

HRID 1530666Notes

Reaction equation

HRID 1530666 reaction equation
CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[CH:8]=[C:9]2[C:18](=[CH:19][C:20]=1[CH3:21])[C:17]1[N:13]([CH:14]=[C:15]([C:22]3[N:26]([CH:27]([CH3:29])[CH3:28])[N:25]=[CH:24][N:23]=3)[N:16]=1)[CH2:12][CH2:11][O:10]2)=O.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:15]2[N:16]=[C:17]3[C:18]4[CH:19]=[C:20]([CH3:21])[C:7]([C:5]5[N:32]([CH:34]6[CH2:39][CH2:38][N:37]([CH3:40])[CH2:36][CH2:35]6)[N:33]=[CH:3][CH:4]=5)=[CH:8][C:9]=4[O:10][CH2:11][CH2:12][N:13]3[CH:14]=2)=[N:23][CH:24]=[N:25]1)([CH3:28])[CH3:29]

Participants

4

Reactant 2

HCID 683128814-Hydrazinyl-1-methylpiperidine hydrochlorideHCID 68312917(2E)-3-(dimethylamino)-1-{13-methyl-4-[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-pentaen-12-yl}prop-2-en-1-one

Product 1

HCID 683131702-(1-isopropyl-1H-1,2,4-triazol-5-yl)-10-methyl-9-(1-(1-methylpiperidin-4-yl)-1H-pyrazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepineYield 26.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2E)-3-(dimethylamino)-1-{13-methyl-4-[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-pentaen-12-yl}prop-2-en-1-one (110 mg, 0.30 mmol) and 4-hydrazinyl-1-methylpiperidine hydrochloride (42 mg, 0.24 mmol) in acetic acid (2.0 mL) was stirred at 100° C. for 1 hour under nitrogen atmosphere. After concentration, the residue was purified by preparative HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to afford 264 (30 mg, 21% yield). LCMS (ESI): RT=5.04 min, m/z: 473.3 [M+H+]. 1H NMR (500 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.00 (s, 1H), 7.94 (s, 1H), 7.58 (d, J=1.5 Hz, 1H), 6.92 (s, 1H), 6.27-6.26 (m, 1H), 5.85 (t, J=13 Hz, 1H), 4.55 (t, J=20 Hz, 4H), 3.76 (s, 1H), 2.86 (s, 2H), 2.19-2.11 (m, 8H), 1.78 (s, 2H), 1.74 (d, J=14.5 Hz, 2H), 4.51 (d, J=7 Hz, 6H)

Workup

  1. concentrationAfter concentration
  2. customthe residue was purified by preparative 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-022fb6a9cecf4cd282767613e21ef117
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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