1-Hydroxybenzotriazole → HCID 178425532, compound

HRID 1093718Notes

Reaction equation

HRID 1093718 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[NH:20][N:19]=[C:18]([C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[CH:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.Cl.[CH3:52][C:53]1[CH:60]=[CH:59][C:56]([C:57]#[N:58])=[CH:55][C:54]=1[NH:61][CH:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1>CN(C=O)C.O>[C:57]([C:56]1[CH:59]=[CH:60][C:53]([CH3:52])=[C:54]([NH:61][CH:62]2[CH2:67][CH2:66][N:65]([C:25](=[O:27])[CH2:24][NH:23][C:21]([C:18]3[CH:17]=[C:16]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:20][N:19]=3)=[O:22])[CH2:64][CH2:63]2)[CH:55]=1)#[N:58]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66591584Benzonitrile, 4-methyl-3-(4-piperidinylamino)-, hydrochloride (1:2)HCID 178525878HCID 178525878, compound

Product 1

HCID 178425532HCID 178425532, compoundYield 22.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (426 mg, 3.3 mmol) was added to a stirred solution of [(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetic acid (285 mg, 1.1 mmol) in DMF (3 mL) followed by HOBt (175 mg, 1.3 mmol) and EDCI.HCl (252 mg, 1.3 mmol). After 2 minutes 4-methyl-3-(piperidin-4-ylamino)-benzonitrile dihydrochloride (250 mg, 1.1 mmol) (prepared according to the method used for the synthesis of Intermediate 3) was added and the stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate and dried over sodium sulfate. The organic layer was concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent) afforded 100 mg (22.7% Yield) of 5-phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-cyano-2-methyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 443.31, 91.96%. 1H NMR (300 MHz, DMSO-d6): δ13.8 (s, 1H), 8.1 (t, 1H), 7.8 (d, 2H), 7.4 (m, 4H), 7.2 (m, 2H), 7.0 (s, 1H), 6.9 (d, 1H), 5.0 (d, 1H), 4.4 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.2 (m, 1H), 2.8 (m, 1H), 2.2 (s, 3H), 2.0 (m, 2H), 1.7 (m, 2H).

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customPurification by column chromatography (using 60-120 silica gel and 5% MeoH in CHCl3 as eluent)

Sources & evidence

ORD record
ord-7a357e1670684d449a40e80c74838dab
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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