Hydrochloric Acid → Biphenyl-2-ylcarbamic Acid 1-[2-(5-(Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}-pentylcarbamoyl)ethyl]piperidin-4-yl Ester

HRID 2109675Notes

Reaction equation

HRID 2109675 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]1)=[O:9].[NH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][N:34]([CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)[CH2:35][C@@H:36]([C:45]1[CH:54]=[CH:53][C:52]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[C:51]2[C:46]=1[CH:47]=[CH:48][C:49](=[O:63])[NH:50]2)[O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39].C(N(C(C)C)CC)(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.Cl>O.CN(C)C=O>[CH2:64]([N:34]([CH2:35][C@@H:36]([C:45]1[CH:54]=[CH:53][C:52]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[C:51]2[C:46]=1[CH:47]=[CH:48][C:49](=[O:63])[NH:50]2)[O:37][Si:38]([C:41]([CH3:42])([CH3:43])[CH3:44])([CH3:40])[CH3:39])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][NH:28][C:19]([CH2:18][CH2:17][N:14]1[CH2:13][CH2:12][CH:11]([O:10][C:8](=[O:9])[NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:16][CH2:15]1)=[O:20])[C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic AcidHCID 669680545-[(R)-2-[(5-Aminopentyl)benzylamino]-1-(tert-butyldimethylsilanyloxy) ethyl]-8-benzyloxy-1H-quinolin-2-one

Product 1

HCID 86608368Biphenyl-2-ylcarbamic Acid 1-[2-(5-(Benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert-butyldimethylsilanyloxy)ethyl]amino}-pentylcarbamoyl)ethyl]piperidin-4-yl EsterYield 91.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of the product of step (e) (3.68 g, 10 mmol) and N,N-dimethylformamide (50 mL) was heated at 60° C. until the solid completely dissolved and then cooled to room temperature. The product of step (d) (6 g, 10 mmol) and diisopropylethylamine (3.5 mL) was added and the reaction mixture was cooled to 0° C. PyBOP (6.25 g, 12 mmol) was added in one portion and the reaction mixture was stirred at 0° C. to room temperature for 2hours. The reaction mixture was then poured into cold water (500 mL) with stirring and the pH of the resulting mixture was adjusted to about 2 using aqueous 1 M hydrochloric acid. This mixture was stirred for 15 min and then filtered to collect the solid, which was washed with water (100 mL) and dried to afford the title compound (8.7 g, HPLC purity >95%) as an off-white solid.

Workup

  1. dissolutioncompletely dissolved
  2. temperaturecooled to room temperature
  3. temperaturethe reaction mixture was cooled to 0° C
  4. stirringwith stirring
  5. stirringThis mixture was stirred for 15 min
  6. filtrationfiltered
  7. customto collect the solid, which
  8. washwas washed with water (100 mL)
  9. customdried

Sources & evidence

ORD record
ord-65677889648f4bd192161ce97ed0790e
Source dataset
uspto-grants-2009_04
Patent number
US07514558B2

Reaction notes

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