Benzoyl chloride → (S)-(4-(1-chloropyrido[3,4-d]pyridazin-4-yl)-2-methylpiperazin-1-yl)(phenyl)methanone

HRID 1514366Notes

Reaction equation

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

Participants

Conditions

Temperature: 25 °C

Procedure

To (S)-1-chloro-4-(3-methylpiperazin-1-yl)pyrido[3,4-d]pyridazine 4 (0.190 g, 0.720 mmol) in dichloromethane (3 ml) was added benzoyl chloride (0.0920 ml, 0.792 mmol) and triethylamine (0.220 ml, 1.58 mmol). The reaction was stirred at 25° C. After 2 h, the reaction contents were poured into saturated sodium bicarbonate (6 mL). The aqueous layer was brought to pH 11 with 5 N NaOH and extracted with 10% methanol in dichloromethane (3×15 mL). Silica gel chromatography (gradient elution 30 to 60% EtOAc in hexanes with 2.5% TEA additive) afforded 210 mg of (S)-(4-(1-chloropyrido[3,4-d]pyridazin-4-yl)-2-methylpiperazin-1-yl)(phenyl)methanone 5. 1H NMR (CDCl3) δ 9.55 (s, 1H), 9.08 (d, J=5.9 Hz, 1H), 8.00 (d, J=5.1 Hz, 1H) 7.41-7.51 (m, 5H) 4.70 (m, 1H), 4.02 (app d, J=11.7 Hz, 1H), 3.86 (app d, J=12.1 Hz, 1H) 3.62-3.72 (m, 1H), 3.47 (dd, J=13.1, 3.3 Hz, 1H), 3.30 (td, J=12.6, 3.3 Hz, 1H), 1.61 (bs, 1H), 1.57 (d, J=6.3 Hz, 3H).

Workup

customthe reaction contents
extractionextracted with 10% methanol in dichloromethane (3×15 mL)
washSilica gel chromatography (gradient elution 30 to 60% EtOAc in hexanes with 2.5% TEA additive)

Sources & evidence

ORD record: ord-952cbbe21efc40a39fa6f19e07cb7513
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222251B2

Reaction notes

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