Hydrochloric Acid → HCID 86586127, compound

HRID 751467Notes

Reaction equation

HRID 751467 reaction equation
C(O[C:6](=[O:35])[NH:7][C@H:8]([C:13](=[O:34])[NH:14][CH:15]1[CH2:21][C:20]([CH3:23])([CH3:22])[CH2:19][N:18]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)(=[O:26])=[O:25])[CH2:17][CH:16]1[OH:33])[CH2:9][CH:10]([CH3:12])[CH3:11])(C)(C)C.Cl.O1CCOCC1.Cl.[O:44]1[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=2[CH:46]=[C:45]1C(O)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>>[OH:33][CH:16]1[CH:15]([NH:14][C:13]([C@@H:8]([NH:7][C:6]([C:45]2[O:44][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][C:47]=3[CH:46]=2)=[O:35])[CH2:9][CH:10]([CH3:12])[CH3:11])=[O:34])[CH2:21][C:20]([CH3:23])([CH3:22])[CH2:19][N:18]([S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)(=[O:25])=[O:26])[CH2:17]1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 10331Benzofuran-2-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 204431481,4-Dioxane hydrochlorideHCID 69313194HCID 69313194, compound

Product 1

HCID 86586127HCID 86586127, compoundYield 62.7%

Procedure

To {(S)-1-[3-Hydroxy-6,6-dimethyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl ester of Example 92h (0.22 g, 0.43 mmol) was added HCl/dioxane (4M, 20 ml, 80 mmol). The mixture was stirred at r.t. for 2 h before solvents and excess amount of HCl was removed on rotavapor. The resulting white solid was dissolved in 5 ml DMF. To the solution was added 2-benzofurancarboxylic acid (84 mg, 0.52 mmol), HBTU (0.2 g, 0.52 mmol) and NMM (0.2 g, 2 mmol). The mixture was stirred at r.t. overnight. DMF was then removed and the residue was redissolved in EtOAc (50 ml), washed with 10% NaHCO3 (50 ml×2) and brine (50 ml). Evaporation of the solvent gave crude product 0.26 g. Purification by column chromatograghy gave the title compound 0.15 g in 63% total yield; MS (M+H+): 556.8; 1H-NMR (400 MHz, CDCl3): •8.66-8.63(m, 1H), 7.94-7.11(m, 10H), 4.72(m, 1H), 4.01-2.98(m, 7H), 1.78-1.39(m, 5H), 1.02-0.85(m, 12H).

Workup

  1. customwas removed on rotavapor
  2. dissolutionThe resulting white solid was dissolved in 5 ml DMF
  3. customDMF was then removed
  4. dissolutionthe residue was redissolved in EtOAc (50 ml)
  5. washwashed with 10% NaHCO3 (50 ml×2) and brine (50 ml)
  6. customEvaporation of the solvent
  7. customgave crude product 0.26 g
  8. customPurification by column chromatograghy

Sources & evidence

ORD record
ord-424206b9642f485f8b4026dccc8edb59
Source dataset
uspto-grants-2008_07
Patent number
US07405209B2

Reaction notes

Loading…