1-Hydroxybenzotriazole → HCID 69545608, compound

HRID 1744683Notes

Reaction equation

HRID 1744683 reaction equation
[C:1]([NH:5][C:6]([C:8]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC([N:28]1[CH2:33][CH2:32][C@@H:31]([C:34](O)=[O:35])[C@H:30]([C:37]2[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=2)[CH2:29]1)=O)(C)(C)C.[ClH:44].CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl.C(=O)(O)[O-].[Na+].[Cl-].[Na+].O>[Cl-:44].[C:1]([NH:5][C:6]([C:8]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[CH2:13][CH2:12][N:11]([C:34]([C@@H:31]2[CH2:32][CH2:33][NH2+:28][CH2:29][C@H:30]2[C:37]2[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=2)=[O:35])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22228444HCID 22228444, compoundHCID 67232495HCID 67232495, compound

Product 1

HCID 69545608HCID 69545608, compoundYield 53.7%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

The product of step D (70 mg) was combined with (3R,4R)-1-(tert-butoxycarbonyl)-3-(4-fluorophenyl)piperidine-4-carboxylic acid (0.1971 mmol; 55 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (57 mg) and 1-hydroxybenzotriazole (40 mg) to which methylene chloride (2.5 mL) was added. The reaction mixture was maintained at ambient temperature for 24 h. The reaction mixture was diluted with methylene chloride (100 mL),washed with a saturated solution of sodium bicarbonate, brine and dried (Na2SO4). The drying agent was removed by filtration and the volatiles were removed in vacuo to furnish the crude N-BOC protected product which was purified on silica gel (eluted with 50:50 to 75:25 ethyl acetate:hexane). The N-BOC protected product was dissolved in ethyl acetate (2 mL) and a saturated solution of hydrogen chloride in ethyl acetate (2 mL) was added. The reaction mixture was maintained at ambient temperature for 90 min. The volatiles were removed in vacuo, the crude product was triturated twice with diethyl ether, and the purified product was dried in vacuo to provide 55 mg of the title compound [MS: m/z 484 (MH+)].

Workup

  1. additionwas added
  2. dry with materialdried (Na2SO4)
  3. customThe drying agent was removed by filtration
  4. customthe volatiles were removed in vacuo
  5. customto furnish the crude N-BOC protected product which
  6. customwas purified on silica gel (eluted with 50:50 to 75:25 ethyl acetate:hexane)
  7. dissolutionThe N-BOC protected product was dissolved in ethyl acetate (2 mL)
  8. additiona saturated solution of hydrogen chloride in ethyl acetate (2 mL) was added
  9. temperatureThe reaction mixture was maintained at ambient temperature for 90 min
  10. customThe volatiles were removed in vacuo
  11. customthe crude product was triturated twice with diethyl ether
  12. customthe purified product was dried in vacuo

Sources & evidence

ORD record
ord-7793446a70e1437ab23e1164f861208c
Source dataset
uspto-grants-2006_03
Patent number
US07015235B2

Reaction notes

Loading…