Acetic Acid → 3-(1,3,4-Thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2(2-amino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 638454ノート

反応式

HRID 638454 の反応式
[S:1]1[CH:5]=[N:4][N:3]=[C:2]1[S:6][CH2:7][C:8]1[CH2:9][S:10][C@@H:11]2[CH:18]([NH:19][C:20](=[O:37])[CH:21]([OH:36])[C:22]3[N:23]=[C:24]([NH:27]C(OC(CC)(C)C)=O)[S:25][CH:26]=3)[C:17](=[O:38])[N:12]2[C:13]=1[C:14]([OH:16])=[O:15].C(O)=O.C(O)(=O)C>C(=O)(O)[O-].[Na+].C([O-])(=O)C>[S:1]1[CH:5]=[N:4][N:3]=[C:2]1[S:6][CH2:7][C:8]1[CH2:9][S:10][C@@H:11]2[CH:18]([NH:19][C:20](=[O:37])[CH:21]([OH:36])[C:22]3[N:23]=[C:24]([NH2:27])[S:25][CH:26]=3)[C:17](=[O:38])[N:12]2[C:13]=1[C:14]([OH:16])=[O:15]

参加物

7

反応物 4

HCID 176Acetic AcidHCID 284Formic AcidHCID 704900353-(1,3,4-Thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)-acetamido]-3-cephem-4-carboxylic acidHCID 178447171HCID 178447171、化合物

生成物 1

HCID 704905123-(1,3,4-Thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2(2-amino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

試薬・触媒・溶媒 2

HCID 175Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

A mixture of 3-(1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)-acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (2.1 g.) and 98 to 100% formic acid (40 ml.) was stirred for 2.5 hours at room temperature. After the reaction, the reaction mixture was concentrated under reduced pressure. The residue was pulverized in acetonitrile, collected by filtration and then washed with ether to produce brown powder (1.3 g.). The powder was dissolved in 5% sodium bicarbonate aqueous solution (20 ml.) and then adjusted to pH 6 with acetic acid. The mixture was subject to neutral almina column chromatography by using pH 5.0 acetate buffer as an eluent. The eluates containing object compound (230 ml.) were collected, adjusted to pH 2.8 to 3.0 with 10% hydrochloric acid, washed with ethyl acetate, and then remaining ethyl acetate was distilled off from the eluates under reduced pressure. The resulting aqueous layer was subjected to column chromatography (Amberlite XAD-4 prepared by Rohm & Haas Co.), and the column was washed with water and then eluted with 20% methanol (80 ml.), 50% methanol (80 ml.) and 70% methanol (300 ml.) in turn. The eluates containing the object compound were collected and then methanol was distilled off under reduced pressure. The remaining aqueous solution was lyophillized to give pale brown powder of 3-(1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-amino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-imino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (0.40 g.), mp. 151° to 180° C. (dec.).

後処理

  1. customAfter the reaction
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. filtrationcollected by filtration
  4. washwashed with ether
  5. customto produce brown powder (1.3 g.)
  6. additionThe eluates containing object compound (230 ml.)
  7. customwere collected
  8. washwashed with ethyl acetate
  9. distillationremaining ethyl acetate was distilled off from the eluates under reduced pressure
  10. customThe resulting aqueous layer was subjected to column chromatography (Amberlite XAD-4 prepared by Rohm & Haas Co.)
  11. washthe column was washed with water
  12. washeluted with 20% methanol (80 ml.), 50% methanol (80 ml.) and 70% methanol (300 ml.) in turn
  13. additionThe eluates containing the object compound
  14. customwere collected
  15. distillationmethanol was distilled off under reduced pressure

出典と根拠

ORDレコード
ord-29326023fc714b569c86608df02788a7
出典データセット
uspto-grants-1985_12
特許番号
US04560765

反応ノート

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