Triethylamine → HCID 86611117, compound

HRID 1012330Notes

Reaction equation

HRID 1012330 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:26]=[CH:25][C:24]([C:27]([NH:29][C@@H:30]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([OH:41])=[CH:37][CH:36]=4)[C:31]([OH:33])=O)=[O:28])=[CH:23][C:9]=3[N:10]3[C:16]=2[C:15]2[CH:17]=[CH:18][C:19]([O:21][CH3:22])=[CH:20][C:14]=2[O:13][CH2:12][CH2:11]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:43][NH:44][O:45][CH3:46].O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[OH:41][C:38]1[CH:39]=[CH:40][C:35]([CH2:34][C@H:30]([NH:29][C:27]([C:24]2[CH:25]=[CH:26][C:8]3[C:7]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)=[C:16]4[N:10]([CH2:11][CH2:12][O:13][C:14]5[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[CH:17][C:15]=54)[C:9]=3[CH:23]=2)=[O:28])[C:31](=[O:33])[N:44]([O:45][CH3:46])[CH3:43])=[CH:36][CH:37]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 58826579HCID 58826579, compound

Product 1

HCID 86611117HCID 86611117, compoundYield 55.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-2-[(12-cyclohexyl-3-methoxy-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carbonyl)amino]-3-(4-hydroxyphenyl)propionic acid (50.0 mg, 0.090 mmol) synthesized in the same manner as in Examples 2-175 and 2-180, N,O -dimethylhydroxylamine hydrochloride (10.5 mg, 0.180 mmol), 1-hydroxybenzotriazole monohydrate (15.2 mg, 0.38 mmol) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (20.7 mg, 0.108 mmol) in N,N-dimethylformamide (1 ml) was added triethylamine (25.1 μl, 0.180 mmol), and the mixture was stirred overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture. The precipitated solid was collected by filtration, further washed with water and dried in vacuo. The obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=1:4). To the obtained residue was added a mixed solvent of hexane:ethyl acetate (5:1), and the precipitated solid was collected by filtration and washed with a mixed solvent of hexane:ethyl acetate (5:1). The obtained solid was dried in vacuo to give N- [(S)-2-(4-hydroxyphenyl)-1-(N-methoxy-N-methylcarbamoyl)ethyl]-12-cyclohexyl-3-methoxy-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxamide (30.0 mg, yield 54.1%).

Workup

  1. filtrationThe precipitated solid was collected by filtration
  2. washfurther washed with water
  3. customdried in vacuo
  4. customThe obtained residue was purified by silica gel chromatography (hexane:ethyl acetate=1:4)
  5. additionTo the obtained residue was added a mixed solvent of hexane:ethyl acetate (5:1)
  6. filtrationthe precipitated solid was collected by filtration
  7. washwashed with a mixed solvent of hexane:ethyl acetate (5:1)
  8. customThe obtained solid was dried in vacuo

Sources & evidence

ORD record
ord-282f1310d2d54e738bd3d489613c49a0
Source dataset
uspto-grants-2011_07
Patent number
US07977331B1

Reaction notes

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