Hydrochloric Acid → 5-((5-Fluoropyridin-2-yl)methoxy)-2-(10-methyl-5,6,7,8,9,10-hexahydropyrido[3',2':4,5]pyrrolo[2,3-d]azepin-2-yl)pyridazin-3(2H)-one hydrochloride

HRID 474980Notes

Reaction equation

HRID 474980 reaction equation
[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][O:10][C:11]2[CH:12]=[N:13][N:14]([C:18]3[CH:19]=[CH:20][C:21]4[C:30]5[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25][C:24]=5[N:23]([CH3:38])[C:22]=4[N:39]=3)[C:15](=[O:17])[CH:16]=2)=[N:7][CH:8]=1>CO.CCOCC>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][O:10][C:11]2[CH:12]=[N:13][N:14]([C:18]3[CH:19]=[CH:20][C:21]4[C:30]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25][C:24]=5[N:23]([CH3:38])[C:22]=4[N:39]=3)[C:15](=[O:17])[CH:16]=2)=[N:7][CH:8]=1

Participants

5

Reactant 2

HCID 313Hydrochloric Acid2×HCID 58093420tert-butyl 2-(4-((5-fluoropyridin-2-yl)methoxy)-6-oxopyridazin-1(6H)-yl)-10-methyl-5,8,9,10-tetrahydropyrido[3',2':4,5]pyrrolo[2,3-d]azepine-7(6H)-carboxylate

Product 1

HCID 668741695-((5-Fluoropyridin-2-yl)methoxy)-2-(10-methyl-5,6,7,8,9,10-hexahydropyrido[3',2':4,5]pyrrolo[2,3-d]azepin-2-yl)pyridazin-3(2H)-one hydrochlorideYield 73%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolvent

Procedure

1.25 M HCl in MeOH (4.0 mL) was added to tert-butyl 2-(4-((5-fluoropyridin-2-yl)methoxy)-6-oxopyridazin-1(6H)-yl)-10-methyl-5,8,9,10-tetrahydropyrido[3′,2′:4,5]pyrrolo[2,3-d]azepine-7(6H)-carboxylate (55 mg, 0.11 mmol), and the resulting solution was stirred under N2 at ambient temperature for 18 h. Additional 1.25 M HCl in MeOH (2.0 mL) was added, and the resulting solution was stirred at ambient temperature for 24 h. The resulting solution was diluted with Et2O (30 mL), and the resulting solids were collected by filtration to provide the title compound (35 mg, 73%) as an off-white powder: mp 226-230° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.12 (s, 2H), 8.64 (d, J=3.0 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.98 (d, J=2.5 Hz, 1H), 7.85 (ddd, J=11.5, 8.5, 2.5 Hz, 1H), 7.72-7.69 (m, 1H), 7.15 (d, J=8.5 Hz, 1H), 6.51 (d, J=3.0 Hz, 1H), 5.30 (s, 2H), 3.71 (s, 3H), 3.45-3.39 (m, 2H), 3.38-3.31 (m, 2H), 3.30-3.28 (m, 2H), 3.15-3.14 (m, 2H); ESI MS m/z 421 [M+H]+; HPLC (Method A) 98.8% (AUC), tR=11.6 min.

Workup

  1. stirringthe resulting solution was stirred at ambient temperature for 24 h
  2. filtrationthe resulting solids were collected by filtration

Sources & evidence

ORD record
ord-09e40487e81641f193d9c4aaea2f354b
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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