4-Methylmorpholine → HCID 178441702, compound

HRID 222531

Reaction equation

HRID 222531 reaction equation
[CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]3[N:31](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:30]=[N:29][N:28]=3)=[CH:17][CH:16]=2)[C:7]([C:11](O)=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].[CH2:51]1[O:55][C@@H:54]2[C@H:56]([O:59][N+:60]([O-:62])=[O:61])[CH2:57][O:58][C@@H:53]2[C@H:52]1[OH:63].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C1C=CN=CC=1.ClCCl>[CH2:1]([C:5]1[N:6]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]3[NH:31][N:30]=[N:29][N:28]=3)=[CH:17][CH:16]=2)[C:7]([C:11]([O:63][C@H:52]2[CH2:51][O:55][C@@H:54]3[C@H:56]([O:59][N+:60]([O-:62])=[O:61])[CH2:57][O:58][C@H:53]23)=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 27661Isosorbide MononitrateHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 467832052-Butyl-4-chloro-1-({2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylic acid2×

Product 1

HCID 178441702HCID 178441702, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-butyl-4-chloro-1-{[2′-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (Step A, Intermediate 4, 7.83 g, 16.5 mmol), isosorbide-5-mononitrate (1.55 g, 8.11 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.78 g, 19.7 mmol), 1-hydroxybenzotriazole (1.25 g, 8.16 mmol), 4-dimethylaminopyridine (0.10 g, 0.82 mmol), and N-methylmorpholine (9.0 mL, 82 mmol) was dissolved in dichloromethane (150 mL) and stirred for 2 days. It was then concentrated in vacuo and purified by reversed-phase mass-directed HPLC (Sunfire C-18) to afford the title compound. 1H NMR (500 MHz, CDCl3) δ 8.02 (dd, J=7.6, 1.0 Hz, 1H), 7.61 (td, J=7.6, 1.3 Hz, 1H), 7.55 (td, J=7.7, 1.1 Hz, 1H), 7.43 (d, J=7.8 Hz, 1H), 7.18 (d, J=7.7 Hz, 2H), 6.96 (d, J=7.8 Hz, 2H), 5.50 (s, 2H), 5.40 (td, J=5.4, 3.0 Hz, 1H), 5.32-5.30 (m, 1H), 4.99 (t, J=5.2 Hz, 1H), 4.51 (d, J=5.0 Hz, 1H), 4.06-4.02 (m, 3H), 3.99 (dd, J=11.4, 5.4 Hz, 1H), 2.68 (t, J=7.7 Hz, 2H), 1.69 (quintet, J=7.7 Hz, 2H), 1.36 (sextet, J=7.5 Hz, 2H), 0.89 (t, J=7.3 Hz, 3H); LC-MS: m/z 610.1 (M+H).

Workup

  1. concentrationIt was then concentrated in vacuo
  2. custompurified by reversed-phase mass-directed HPLC (Sunfire C-18)

Sources & evidence

ORD record
ord-0b106e23f0524819891a6dadd4e67d72
Source dataset
uspto-grants-2012_06
Patent number
US08207208B2

Linked notes

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