Morpholine → 11-(3-Chloro-4-fluorobenzyl)-9-methoxy-2-(2-morpholin-4-ylethyl)-3,4,5,6,12,13-hexahydro-2h[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,8,10(11h)-trione

HRID 18021Notes

Reaction equation

HRID 18021 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][C:35]=1[F:36])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:30][CH3:31])[C:10](=[O:29])[N:11]3[CH2:21][CH2:20][CH2:19][CH2:18][N:17]([CH2:22][CH2:23]S(C)(=O)=O)[C:16](=[O:28])[C:12]3=2)[C:7]1=[O:32].[NH:37]1[CH2:42][CH2:41][O:40][CH2:39][CH2:38]1.C(N(C(C)C)CC)(C)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][C:35]=1[F:36])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:30][CH3:31])[C:10](=[O:29])[N:11]3[CH2:21][CH2:20][CH2:19][CH2:18][N:17]([CH2:22][CH2:23][N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[C:16](=[O:28])[C:12]3=2)[C:7]1=[O:32]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 66997670HCID 66997670, compound

Product 1

HCID 6699789611-(3-Chloro-4-fluorobenzyl)-9-methoxy-2-(2-morpholin-4-ylethyl)-3,4,5,6,12,13-hexahydro-2h[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,8,10(11h)-trione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 11-(3-chloro-4-fluorobenzyl)-9-methoxy-2-(2-methane-sulfonylethyl)-3,4,5,6,12,13-hexahydro-2H[1,4]diazocino[2,1-a]-2,6-naphthyridine-1,8,10(1H)-trione (97 mg, 0.17 mmol), morpholine (30 mg, 0.35 mmol), and diisopropylethylamine (006 mL, 0.355 mmol) in THF (1.7 mL) was stirred at 40° C. overnight. The product mixture was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with gradient mixture of methanol in dichloromethane. Collection and concentration of appropriate fractions afforded the title compound. 1H NMR (400 MHz, CDCl3) δ 7.37 (dd, J=2.0, 7.0 Hz, 1H), 7.21 (m, 1H), 7.12 (t, J=8.8 Hz, 1H), 4.80 (dd, J=6.2, 13.9 Hz, 1H), 4.74 (d, J=15.0 Hz, 1H), 4.62 (d, J=14.8 Hz, 1H), 4.12-4.07 (m, 4H), 3.69-3.64 (m, 4H), 3.45-3.30 (m, 5H), 3.20-3.13 (m, 1H), 2.90-2.83 (m, 1H), 2.66-2.42 (m, 7H), 2.08 (br m, 1H), 1.91-1.72 (br m, 3H). (ES MS M+1=547.4)

Workup

  1. concentrationThe product mixture was concentrated under vacuum
  2. additionThe residue was subjected to column chromatography on silica gel eluting with gradient mixture of methanol in dichloromethane
  3. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-4515af7338a040a98ba7874ecbe8ed6d
Source dataset
uspto-grants-2010_06
Patent number
US07741315B2

Reaction notes

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