Succinic anhydride → 5'-O-(3-Carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine

HRID 982161

反応式

HRID 982161 の反応式
Cl.[F:2][C:3]1([F:19])[C@H:7]([OH:8])[C@@H:6]([CH2:9][OH:10])[O:5][C@H:4]1[N:11]1[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]1=[O:13].[C:20]1(=[O:26])[O:25][C:23](=[O:24])[CH2:22][CH2:21]1>N1C=CC=CC=1>[C:23]([CH2:22][CH2:21][C:20]([O:10][CH2:9][C@H:6]1[O:5][C@@H:4]([N:11]2[CH:18]=[CH:17][C:15]([NH2:16])=[N:14][C:12]2=[O:13])[C:3]([F:2])([F:19])[C@@H:7]1[OH:8])=[O:26])([OH:25])=[O:24]

参加物

4

反応物 2

HCID 7922Succinic anhydrideHCID 60749Gemcitabine Hydrochloride

生成物 1

HCID 98204035'-O-(3-Carboxy-1-oxopropyl)-2'-deoxy-2',2'-difluorocytidine

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

実験手順

A 600 mg portion of dry 2'-deoxy-2',2'-difluorocytidine, hydrochloride, was added to 6 ml of dry pyridine, and 804 mg of succinic anhydride was added. The reaction mixture was stirred at ambient temperature for 1.5 hours. The mixture was then concentrated to an oil under vacuum, and the oil was stored overnight in the freezer. It was then allowed to stand at ambient temperature for 4 hours, and was chromatographed over a 500 ml Q-Sepharose column (Pharmacia Inc.). The oil was dissolved in 6 ml of 0.lM ammonium acetate buffer, and was passed over the column, eluting with a gradient buffer which changed from 0.lM to 1.0M ammonium acetate, at pH 8.0 at all times. Analytical chromatography of the mixture on a small mono-Q column showed that bisacylated and tris-acylated products were present, as well as mono-acylated product and a small amount of starting material. The product-containing fractions, amounting to about 200 ml, were placed in a 37° C. bath, for 68 hours. At the end of that time, the tris-acylated product had been decomposed and both mono- and bisacylated products were still present.

後処理

  1. additionwas added
  2. concentrationThe mixture was then concentrated to an oil under vacuum
  3. waitthe oil was stored overnight in the freezer
  4. waitto stand at ambient temperature for 4 hours
  5. customwas chromatographed over a 500 ml Q-Sepharose column (Pharmacia Inc.)
  6. dissolutionThe oil was dissolved in 6 ml of 0.lM ammonium acetate buffer
  7. washeluting with a gradient buffer which
  8. customwere placed in a 37° C.
  9. waitfor 68 hours

出典と根拠

ORDレコード
ord-22a5aac8fcf74bcab8283f0dd0bfc551
出典データセット
uspto-grants-1991_02
特許番号
US04994558

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