1-Hydroxybenzotriazole → HCID 178523544, compound

HRID 1177960Notes

Reaction equation

HRID 1177960 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[NH2:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])[CH2:23][CH2:22]1)=[O:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[OH:61][C:62]1[CH:70]=[CH:69][C:65]([C:66](O)=[O:67])=[CH:64][N:63]=1>CN(C=O)C.O>[OH:61][C:62]1[CH:70]=[CH:69][C:65]([C:66]([NH:17][CH2:18][C:19](=[O:20])[N:21]2[CH2:22][CH2:23][N:24]([C:27](=[O:38])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]2)=[O:67])=[CH:64][N:63]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA saltHCID 178418479HCID 178418479, compound

Product 1

HCID 178523544HCID 178523544, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (56 mg, 0.43 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt. (74 mg, 0.17 mmol) in DMF (1 mL). HOBT (23 mg, 0.17 mmol) and EDCI.HCl (33 mg, 0.17 mmol) were then added at room temperature. After 2 minutes, 6-hydroxy nicotinic acid (20 mg, 0.14 mmol) was added and the resulting mixture was stirred at room temperature for 4 hrs. Cold water (20 mL) was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford 35 mg (56.5% yield) of 6-hydroxy-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-nicotinamide. LCMS Purity: 99.38%, HPLC Purity: 92.66%, 1H NMR (DMSO-d6): δ 12 (s, 1H), 8.0 (t, 1H), 7.9-7.8 (m, 2H), 7.8-7.7 (d, 1H), 7.7-7.6 (t, 1H), 7.6-7.5 (m, 1H), 6.4-6.3 (dd, 1H), 4.2-4.0 (m, 2H), 3.8-3.7 (m, 2H), 3.6 (m, 2H), 3.4 (m, 2H), 3.2-3.1 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-86ac947cf9d5431a8b56c3526b345c24
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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