1-Hydroxybenzotriazole → HCID 57874365, compound

HRID 1093827Notes

Reaction equation

HRID 1093827 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:22])[CH2:18][C:19]([OH:21])=O)=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH:52]1[CH2:57][CH2:56][CH:55]([O:58][C:59]2[CH:60]=[C:61]([CH:64]=[CH:65][CH:66]=2)[C:62]#[N:63])[CH2:54][CH2:53]1>CN(C=O)C.O>[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:22])[CH2:18][C:19]([N:52]2[CH2:53][CH2:54][CH:55]([O:58][C:59]3[CH:66]=[CH:65][CH:64]=[C:61]([C:62]#[N:63])[CH:60]=3)[CH2:56][CH2:57]2)=[O:21])=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 534337453-[(Piperidin-4-yl)oxy]benzonitrile--hydrogen chloride (1/1)HCID 55049154N-biphenyl-4-yl-malonamic acid

Product 1

HCID 57874365HCID 57874365, compoundYield 20.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (135 mg, 11.0 mmol) was added to a stirred solution of N-biphenyl-4-yl-malonamic acid (64 mg, 0.3 mmol) in DMF (2.0 mL) followed by HOBt (61 mg, 0.45 mmol) and EDCI.HCl (85 mg, 0.45 mmol). After 2 minutes of stirring, 3-(piperidin-4-yloxy)-benzonitrile hydrochloride (60 mg, 0.3 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethylacetate, washed with brine and concentrated The residue was purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3) to afford 27 mg (19.7% Yield) of N-biphenyl-4-yl-3-[4-(3-cyano-phenoxy)-piperidin-1-yl]-3-oxo-propionamide. LC/MS [M+H]+: 440.2, 98.14%, 1H NMR (300 MHz, DMSO-d6): δ10.2 (s, 1H), 7.7 (m, 5H), 7.5 (m, 5H), 7.3 (m, 2H), 4.8 (m, 1H), 4.0 (m, 1H), 3.8 (m, 1H), 3.6 (m, 2H), 3.3 (m, 2H), 2.0 (m, 2H), 1.7 (m, 1H), 1.6 (m, 1H).

Workup

  1. additionwas added
  2. stirringstirring
  3. waitwas continued at ambient temperature overnight
  4. extractionextracted with ethylacetate
  5. washwashed with brine
  6. concentrationconcentrated The residue
  7. customwas purified by column chromatography (using neutral alumina and 5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-54e58774c2b64d0999f006d46eb8a40a
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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