2-Methylbut-3-yne-1,2-diol → (+/-)-9-(3,4-Dihydroxy-3-methyl-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo azulene-2-carboxylic acid amide

HRID 575088ノート

反応式

HRID 575088 の反応式
Br[C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]([NH2:17])=[O:16])=[N:8][C:7]=3[C:6]=2[CH:18]=1.[CH3:20][C:21]([OH:26])([C:24]#[CH:25])[CH2:22][OH:23]>CS(C)=O.C(N(CC)CC)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:26][C:21]([CH3:20])([CH2:22][OH:23])[C:24]#[C:25][C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:14][CH2:13][CH2:12][C:11]3[S:10][C:9]([C:15]([NH2:17])=[O:16])=[N:8][C:7]=3[C:6]=2[CH:18]=1

参加物

7

反応物 2

HCID 221369052-Methylbut-3-yne-1,2-diolHCID 866930599-Bromo-8-fluoro-4,5-dihydro-[1]benzoxepino[5,4-d]thiazole-2-carboxamide

生成物 1

HCID 86693117(+/-)-9-(3,4-Dihydroxy-3-methyl-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo azulene-2-carboxylic acid amide

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8471Triethylamine溶媒

実験手順

The title compound was prepared according to a procedure similar to that described in Procedure G. Into a 8-mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed a suspension of 9-Bromo-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide (200 mg, 0.58 mmol, 1.00 equiv), 2-methylbut-3-yne-1,2-diol (200 mg, 2.00 mmol, 3.50 equiv) and Pd(PPh3)2Cl2 (40 mg, 0.06 mmol, 0.10 equiv) in DMSO (1 mL) and triethylamine (1 mL). The final reaction mixture was irradiated with microwave radiation for 1 h at 70° C. The resulting solution was diluted with 20 mL, of water. The solids were collected by filtration and washed by acetonitrile (10 mL). This resulted in 30 mg (14%) of 9-(3,4-Dihydroxy-3-methyl-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a light brown solid. LC-MS (ES, m/z): 363[M+H]+; 1H-NMR (300 MHz, DMSO-d6, ppm) δ 8.64 (d, 1H), 8.438 (br s, 1H), 7.873 (br s, 1H), 6.997 (d, 1H), 5.397 (s, 1H), 4.971 (t, 1H), 4.383 (t, 2H), 3.510-3.380 (m, 4H), 1.426 (s, 3H).

後処理

  1. customInto a 8-mL sealed tube
  2. custompurged
  3. temperaturemaintained with an inert atmosphere of nitrogen
  4. customThe final reaction mixture
  5. customwas irradiated with microwave radiation for 1 h at 70° C
  6. filtrationThe solids were collected by filtration
  7. washwashed by acetonitrile (10 mL)
  8. customThis resulted in 30 mg (14%) of 9-(3,4-Dihydroxy-3-methyl-but-1-ynyl)-8-fluoro-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid amide as a light brown solid

出典と根拠

ORDレコード
ord-53de05fecc944ae6b712fd6aa50d793f
出典データセット
uspto-grants-2015_05
特許番号
US09034866B2

反応ノート

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