4-Methylmorpholine → HCID 18712865, compound

HRID 279244Notes

Reaction equation

HRID 279244 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C@H:15]([N:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:18]([C:29](O)=[O:30])[CH2:17]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:32]=1.[Na].[N:34]1([CH2:39][CH2:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][NH:42]2)[CH:38]=[CH:37][N:36]=[CH:35]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C@H:15]([N:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[C@@H:18]([C:29]([N:42]4[CH2:43][CH2:44][CH2:45][CH2:46][CH:41]4[CH2:40][CH2:39][N:34]4[CH:38]=[CH:37][N:36]=[CH:35]4)=[O:30])[CH2:17]3)[C:10]3=[N:11][CH:12]=[CH:13][CH:14]=[C:9]3[CH2:8][CH2:7][C:6]=2[CH:32]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226629092-[2-(1H-Imidazol-1-yl)ethyl]piperidineHCID 69691675HCID 69691675, compound

Product 1

HCID 18712865HCID 18712865, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

Sodium 1,1-dimethylethyl 4-(8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(S)-yl)-2(R)-carboxy-1-piperazinecarboxylate (prepared as described in Preparative Example 6 (sodium salt)) (0.5239 g, 1.09 mmoles), 2-[2-(1H-imidazol-1-yl)ethyl]piperidine (prepared as described in Preparative Example 57, Step D) (0.2544 g, 1.42 mmoles), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.272 g, 1.42 mmoles), 1-hydroxybenzotriazole (0.1918 g, 1.42 mmoles) and 4-methylmorpholine (0.156mL, 1.42 mmoles) were dissolved in anhydrous DMF (23.5 mL) and the mixture was stirred under argon at 25° C. for 286 h. The solution was evaporated to dryness and the residue was taken up in dichloromethane and washed with 1N NaOH, dried (MgSO4), filtered and evaporated to dryness. The residue was chromatographed on silica gel using 2.5% (10% conc. NH4OH in methanol)-dichloromethane as the eluant to give the title compound (0.2298 g, 32%): HRFABMS: m/z 619.3169 (MH+) (Calcd. m/z 691.3163).

Workup

  1. customThe solution was evaporated to dryness
  2. washwashed with 1N NaOH
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was chromatographed on silica gel using 2.5% (10% conc. NH4OH in methanol)-dichloromethane as the eluant

Sources & evidence

ORD record
ord-ca979f0680d84319ab4b136f3cfc663f
Source dataset
uspto-grants-2002_03
Patent number
US06362188B1

Reaction notes

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