Hydrochloric Acid → 4-(4-Fluorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride

HRID 475007Notes

Reaction equation

HRID 475007 reaction equation
[F:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:4][CH:3]=1.[ClH:39]>ClCCl>[ClH:39].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][NH:27][CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:37][CH:38]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 70805234tert-butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate

Product 1

HCID 668738824-(4-Fluorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochlorideYield 38%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 8-(4-(4-fluorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H) carboxylate (120 mg, 0.23 mmol) in dichloromethane (1.0 mL) was added HCl (2M in diethyl ether, 5.0 mL). The resulting slurry was stirred at room temperature overnight and concentrated under reduced pressure. The residue was purified by semi-preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.20 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA). The clean fractions were combined and concentrated under reduced pressure. The trifluoracetate salt was converted to HCl salt by dissolving in 1.25 M HCl in methanol and concentrating the resulting solution to dryness. This process was repeated three times to afford the title compound (40.0 mg, 38%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.63 (d, J=8.5 Hz, 1H), 7.57 (d, J=7.5 Hz, 1H), 7.51 (dd, J=8.5, 5.5 Hz, 2H), 7.44 (s, 1H), 7.15 (t, J=8.5 Hz, 2H), 7.06 (dd, J=8.5, 2.0 Hz, 1H), 6.28 (dd, J=7.5, 3.0 Hz, 1H), 6.12 (d, J=3.0 Hz, 1H), 5.16 (s, 2H), 4.55 (s, 2H), 3.77 (s, 3H), 3.58 (t, J=5.5 Hz, 2H), 3.20 (t, J=5.5 Hz, 2H), 2.23-2.19 (m, 2H); ESI MS m/z 418 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by semi-preparative HPLC (Phenomenex Luna C18 (2), 250.0×21.20 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA)
  3. concentrationconcentrated under reduced pressure
  4. dissolutionby dissolving in 1.25 M HCl in methanol
  5. concentrationconcentrating the resulting solution to dryness

Sources & evidence

ORD record
ord-ccc30b255efa48cda9788c254ea65d6f
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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