Hydrochloric Acid → (R)-N-Hydroxy-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-butyramide hydrochloride

HRID 1184016ノート

反応式

HRID 1184016 の反応式
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][N:18]([CH2:21][CH2:22][C@:23]([S:35]([CH3:38])(=[O:37])=[O:36])([CH3:34])[C:24]([NH:26][O:27]C4CCCCO4)=[O:25])[C:17](=[O:39])[CH:16]=3)=[CH:11][CH:10]=2)[CH2:5][CH2:4]1.[ClH:40].O1CCOCC1>C(Cl)Cl.CO>[ClH:40].[OH:27][NH:26][C:24](=[O:25])[C@@:23]([S:35]([CH3:38])(=[O:37])=[O:36])([CH3:34])[CH2:22][CH2:21][N:18]1[CH:19]=[CH:20][C:15]([C:12]2[CH:11]=[CH:10][C:9]([N:6]3[CH2:7][CH2:8][CH:3]([CH2:2][OH:1])[CH2:4][CH2:5]3)=[CH:14][CH:13]=2)=[CH:16][C:17]1=[O:39]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86671966HCID 86671966、化合物

生成物 1

HCID 86671964(R)-N-Hydroxy-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-butyramide hydrochloride

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

(R)-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-butyramide (85.1 mg, 0.152 mmol) was dissolved in methylene chloride (5 mL) at ambient temperature. To this solution was added 4M HCl in 1,4-dioxane (0.304 mL, 1.22 mmol) and methanol (1 ml). The resulting solution was stirred at ambient temperature for 45 minutes. The solution was concentrated to a crude residue in vacuo. To the residue was added ethyl acetate (10 ml) and the resulting slurry was stirred overnight at ambient temperature. The slurry was filtered and washed with ethyl acetate/heptanes (1:1). The solid was dried in vacuo to afford (R)—N-Hydroxy-4-{4-[4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-2-oxo-2H-pyridin-1-yl}-2-methanesulfonyl-2-methyl-butyramide hydrochloride as an off-white solid. (72.7 mg). LCMS: M+1 478.6. 1H NMR (CD3OD, 400 MHZ) dppm, 7.82 (2H, d), 7.79 (1H, d), 6.84 (1H, d), 6.80-6.77 (1H, dd), 4.35-4.28 (1H, m), 4.00-3.93 (1H, m), 3.79-3.72 (4H, m), 3.55 (2H, d), 3.09 (3H, s), 2.64-2.56 (1H, m), 2.40-2.33 (1H, m), 2.16-2.13 (2H, d), 2.00-1.92 (1H, m), 1.87-1.76 (2H, m), 1.70 (3H, s).

後処理

  1. concentrationThe solution was concentrated to a crude residue in vacuo
  2. additionTo the residue was added ethyl acetate (10 ml)
  3. stirringthe resulting slurry was stirred overnight at ambient temperature
  4. filtrationThe slurry was filtered
  5. washwashed with ethyl acetate/heptanes (1:1)
  6. customThe solid was dried in vacuo

出典と根拠

ORDレコード
ord-aa01e21f58384df78840cf6475d17049
出典データセット
uspto-grants-2014_03
特許番号
US08664401B2

反応ノート

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