Hydrochloric Acid → 5-Methoxy-benzofuran-2-carboxylic acid {(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-amide

HRID 1790605Notes

Reaction equation

HRID 1790605 reaction equation
C([O:5][C:6](=O)[NH:7][C@H:8]([C:13](=[O:33])[NH:14][CH:15]1[CH2:21][CH:20]([CH3:22])[CH2:19][N:18]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:25])=[O:24])[CH2:17][CH:16]1[OH:32])[CH2:9][CH:10]([CH3:12])[CH3:11])(C)(C)C.Cl.O1CCOCC1.Cl.[CH3:43][O:44][C:45]1[CH:46]=[CH:47][C:48]2[O:52][C:51](C(O)=O)=[CH:50][C:49]=2[CH:56]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>>[OH:32][CH:16]1[CH:15]([NH:14][C:13]([C@@H:8]([NH:7][C:6]([C:51]2[O:52][C:48]3[CH:47]=[CH:46][C:45]([O:44][CH3:43])=[CH:56][C:49]=3[CH:50]=2)=[O:5])[CH2:9][CH:10]([CH3:11])[CH3:12])=[O:33])[CH2:21][CH:20]([CH3:22])[CH2:19][N:18]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)(=[O:25])=[O:24])[CH2:17]1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 2886385-Methoxybenzofuran-2-carboxylic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11496976{(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl esterHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 866074165-Methoxy-benzofuran-2-carboxylic acid {(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-amideYield 69%

Procedure

To {(S)-1-[3-hydroxy-6-methyl-1-(pyridine-2-sulfonyl)-azepan-4-ylcarbamoyl]-3-methyl-butyl}-carbamic acid tert-butyl ester (0.13 g, 0.28 mmol) was added HCl/dioxane (4M, 2.8 ml, 11.2 mmol). The mixture was stirred at RT for 2 h before solvents and excess amount of HCl was removed on rotavapor. The result white solid was dissolved in 5 ml DMF. To the solution was added 5-methoxy-benzofuran-2-carboxylic acid (63.4 mg, 0.33 mmol), HBTU (125 g, 0.33 mmol) and NMM (0.14 g, 1.34 mmol). The mixture was stirred at RT overnight. DMF was then removed and the residue was re-dissolved in EtOAc (50 ml), washed with 10% NaHCO3 (50 ml×2) and brine (50 ml). The combined organics were concentrated by rotary evaporation. Purification by column chromatograghy gave the title compound (110 mg in 69% yield, 2 steps): MS (M+H+):573.4; 1H-NMR (400 Hz, CDCl3): d=8.74–8.66(dd, 1H), 7.96–6.97(m, 9H), 4.72(m, 1H), 4.18–3.21(m, 7H), 2.81(m, 1H), 2.04–1.74(m, 6H), 1.25(m, 2H), 0.99–0.87(m, 9H).

Workup

  1. customwas removed on rotavapor
  2. dissolutionThe result white solid was dissolved in 5 ml DMF
  3. customDMF was then removed
  4. dissolutionthe residue was re-dissolved in EtOAc (50 ml)
  5. washwashed with 10% NaHCO3 (50 ml×2) and brine (50 ml)
  6. concentrationThe combined organics were concentrated by rotary evaporation
  7. customPurification by column chromatograghy

Sources & evidence

ORD record
ord-3648588902864b24ab08bf9b5bb518bc
Source dataset
uspto-grants-2006_07
Patent number
US07071184B2

Reaction notes

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