(R)-1-Boc-3-methylpiperazine → HCID 57657604, compound

HRID 1514393Notes

Reaction equation

Cl[C:2]1[C:3]2[N:17]=[CH:16][CH:15]=[CH:14][C:4]=2[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[N:6][N:7]=1.[CH3:18][C@H:19]1[NH:24][CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20]1>C(Cl)Cl>[CH3:18][C@H:19]1[N:24]([C:2]2[C:3]3[N:17]=[CH:16][CH:15]=[CH:14][C:4]=3[C:5]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[N:6][N:7]=2)[CH2:23][CH2:22][N:21]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[CH2:20]1

Participants

Conditions

Temperature: 130 °C

Procedure

8-chloro-5-phenylpyrido[3,2-d]pyridazine 71 (374 mg, 1.548 mmol) and (R)-tert-butyl 3-methylpiperazine-1-carboxylate (1240 mg, 6.19 mmol) were combined in a reaction vial and heated to 130° C. for 3 h. After cooling to room temperature, the resulting solid was dissolved in 100 mL of CH2Cl2 and washed with 1×10 mL of saturated NaHCO3, followed by 1×10 mL of brine. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification by column chromatography afforded pure (R)-tert-butyl 3-methyl-4-(5-phenylpyrido[3,2-d]pyridazin-8-yl)piperazine-1-carboxylate 74. 1H-NMR (400 MHz, CDCl3): δ 9.08 (dd, J=4.3, 1.6 Hz, 1H), 8.32 (dd, J=8.2, 1.6 Hz, 1H), 7.70 (m, 2H), 7.67 (dd, J=8.6, 4.3 Hz, 1H), 7.53 (m, 3H), 4.70 (m, 1H), 4.30-3.67 (series of m, 2H), 3.66 (ddd, J=13.3, 12.1, 3.5 Hz, 1H), 3.35 (m, 2H), 1.51 (s, 9H), 1.36 (br d, J=6.3 Hz, 3H). MS 405.2 (calc'd) 406.1 (M+H, found).

Workup

temperatureAfter cooling to room temperature
washwashed with 1×10 mL of saturated NaHCO3
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography

Sources & evidence

ORD record: ord-7ffab96760ce4961b9ff01d5e72fe8e7
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222251B2

Reaction notes

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