4-Methylmorpholine → HCID 24958723, compound

HRID 1173001Notes

Reaction equation

HRID 1173001 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]3[N:27]=[N:26][N-:25][N:24]=3)=[CH:15][CH:16]=2)[C:8]([CH2:28][OH:29])=[C:7]([Cl:30])[N:6]=1.[K+].[N+:32]([O:35][C@@H:36]([CH2:43][O:44][N+:45]([O-:47])=[O:46])[CH2:37][CH2:38][CH2:39][C:40](O)=[O:41])([O-:34])=[O:33].CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.OP([O-])(O)=O.[Na+].OP([O-])([O-])=O.[Na+].[Na+]>CN(C)C1C=CN=CC=1.CO.ClCCl.ClCCl>[N+:32]([O:35][C@@H:36]([CH2:43][O:44][N+:45]([O-:47])=[O:46])[CH2:37][CH2:38][CH2:39][C:40]([O:29][CH2:28][C:8]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]3[N:24]=[N:25][NH:26][N:27]=3)=[CH:15][CH:16]=2)[C:5]([CH2:4][CH2:3][CH2:2][CH3:1])=[N:6][C:7]=1[Cl:30])=[O:41])([O-:34])=[O:33]

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 11476710Losartan potassium saltHCID 29923590HCID 29923590, compoundHCID 86630341Sodium phosphate (Na3(PO4)2)

Product 1

HCID 24958723HCID 24958723, compoundYield 74.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a dichloromethane (50 mL) suspension of Losartan potassium (4.72 g, 10.24 mmol), (5R)-5,6-bis(nitrooxy)hexanoic acid (1.23 g, 5.16 mmol), and 4-dimethylaminopyridine (0.075 g, 0.614 mmol) was added N-methylmorpholine (1.2 mL, 10.91 mmol), followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.2 g, 6.26 mmol). After 2 hours, the reaction mixture was mixed with pH 5 buffer (sodium phosphate monobasic/sodium phosphate dibasic, 250 mL) and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (magnesium sulfate), and concentrated in vacuo. Chromatography over silica eluting with 2-12% methanol/dichloromethane afforded the title compound as a white solid (2.485 g, 3.86 mmol, 74.8% yield). 1H NMR (500 MHz, CD3CN) δ 7.69 (dd, J=1.1, 7.6 Hz, 1H), 7.64 (dt, J=1.3, 7.6 Hz, 1H), 7.53 (dt, J=1.1, 7.6 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.09 (d, J=8.3 Hz, 2H), 6.91 (d, J=8.3 Hz, 2H), 5.27 (dq, J=2.8, 6.3 Hz, 1H), 5.15 (s, 2H), 4.95 (s, 2H), 4.75 (dd, J=2.8, 12.8 Hz, 1H), 4.51 (dd, J=6.1, 12.9 Hz, 1H), 2.48 (t, J=7.7 Hz, 2H), 2.08 (t, J=7.3 Hz, 2H), 1.5-1.7 (m, 6H), 1.28 (pent, J=7.4 Hz, 2H), 0.83 (t, J=7.5 Hz, 3H). LCMS: m/e 643.2 (M+H).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (magnesium sulfate)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-06b9e92d654c4be9b3fb7962f20f2eb4
Source dataset
uspto-grants-2010_11
Patent number
US07834042B2

Reaction notes

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