Lithium Hexamethyldisilazide → 9-Benzenesulfonyl-3-chloro-5-hydroxy-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrile

HRID 60232ノート

反応式

HRID 60232 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C[O:12][C:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([Cl:24])[CH:22]=2)[N:17]([S:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[O:27])=[O:26])[C:16]=1[CH2:34][N:35]([CH2:46][C:47]#[N:48])S(C1C=CC(C)=CC=1)(=O)=O)=O>C1COCC1>[C:28]1([S:25]([N:17]2[C:16]3[CH:34]=[N:35][C:46]([C:47]#[N:48])=[C:13]([OH:12])[C:15]=3[C:23]3[CH:22]=[C:21]([Cl:24])[CH:20]=[N:19][C:18]2=3)(=[O:27])=[O:26])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

参加物

4

反応物 2

HCID 2733832Lithium HexamethyldisilazideHCID 583650861-Benzenesulfonyl-5-chloro-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]-methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester

生成物 1

HCID 583649529-Benzenesulfonyl-3-chloro-5-hydroxy-9H-diprido[2,3-b;4',3'-d]pyrrole-6-carbonitrile収率 27.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

Lithium bis(trimethylsilyl)amide (220 mL of a 1N solution in THF, 220 mmol) was added dropwise to a cooled (−78° C.) suspension of 1-benzenesulfonyl-5-chloro-2-{[cyanomethyl-(toluene-4-sulfonyl)amino]methyl}-1H-pyrrolo[2,3-b]pyridine-3-carboxylic acid methyl ester (39.6 g, 69.1 mmol) in dry THF (350 mL). The reaction mixture was allowed to slowly warm to −10° C. then slowly quenched into cold 1M hydrochloric acid. The layers were separated and the aqueous layer further extracted with THF. The combined organic layer was washed with brine, dried (Na2SO4), filtered and evaporated. The resultant residue was triturated with methanol then acetone and air dried to afford the title compound as a tan solid (7.37 g, 27%). LCMS (Method B): RT=5.11 min, M+H+=385/387. 1H NMR (400 MHz, DMSO-d6): 9.23 (s, 1H), 8.76 (d, J=2.4 Hz, 1H), 8.69 (d, J=2.4 Hz, 1H), 8.19-8.19 (m, 2H), 7.75-7.75 (m, 1H), 7.62-7.61 (m, 2H).

後処理

  1. temperaturea cooled
  2. customthen slowly quenched into cold 1M hydrochloric acid
  3. customThe layers were separated
  4. extractionthe aqueous layer further extracted with THF
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe resultant residue was triturated with methanol
  10. dry with materialacetone and air dried

出典と根拠

ORDレコード
ord-b75397902a0d4ec9bd439520203c8663
出典データセット
uspto-grants-2016_09
特許番号
US09440976B2

反応ノート

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