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 229788

反応式

HRID 229788 の反応式
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

参加物

7

反応物 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

生成物 1

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

実験手順

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)

後処理

  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

出典と根拠

ORDレコード
ord-8bb701dc1d4a4713a1bb87f39fee1c71
出典データセット
uspto-grants-2009_07
特許番号
US07563784B2

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