2-(5-Methylisoxazol-3-yl)but-3-yn-2-ol → (5)-10-(3-Hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

HRID 575087ノート

反応式

HRID 575087 の反応式
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([OH:11])([C:9]#[CH:10])[CH3:8])[CH:3]=1.Br[C:13]1[CH:26]=[C:25]2[C:16]([O:17][CH2:18][CH2:19][N:20]3[C:24]2=[N:23][C:22]([C:27]([NH2:29])=[O:28])=[CH:21]3)=[CH:15][CH:14]=1>CS(C)=O.C(N(CC)CC)C.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:11][C@@:7]([C:4]1[CH:3]=[C:2]([CH3:1])[O:6][N:5]=1)([CH3:8])[C:9]#[C:10][C:13]1[CH:14]=[CH:15][C:16]2[O:17][CH2:18][CH2:19][N:20]3[C:24](=[N:23][C:22]([C:27]([NH2:29])=[O:28])=[CH:21]3)[C:25]=2[CH:26]=1

参加物

6

反応物 2

HCID 582217592-(5-Methylisoxazol-3-yl)but-3-yn-2-olHCID 6831288310-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

生成物 1

HCID 86693116(5)-10-(3-Hydroxy-3-(5-methylisoxazol-3-yl)but-1-yn-1-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 679Dimethyl Sulfoxide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 2-(5-methylisoxazol-3-yl)but-3-yn-2-ol (515 mg, 3.41 mmol, 3.50 equiv), 13-bromo-9-oxa-3,6-diazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene-4-carboxamide (300 mg, 0.97 mmol, 1 equiv) and Pd(PPh3)2Cl2 (205 mg, 0.29 mmol, 0.3 equiv) in DMSO (2 mL) and triethylamine (2 mL). The final reaction mixture was irradiated with microwave radiation for 2 h at 70° C. The resulting mixture was washed with 1×100 mL of water and 2×100 mL of CH3CN. The solids were collected by filtration. The residue was further purified by Chiral-Prep-HPLC with the following conditions (2#-Gilson Gx 281(HPLC-09): Column, Chiralpak IA2*25 cm, 5 um Chiral-P(IA)004IA00CJ-MB003; Phase A:MTBE Phase B:EtOH (0.2% DEA)-HPLC (10.0% EtOH for 60 min, then down to 0%); Detector, uv 254/220 nm. This resulted in 34.2 mg (9%) of 9-[(S)-3-Hydroxy-3-(5-methyl-isoxazol-3-yl)-but-1-ynyl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid LC-MS (ES, m/z): 379[M+H]+; 1H-NMR (400 MHz, DMSO-d6, ppm): δ 8.536 (s, 1H), 7.802 (s, 1H), 7.558 (br s, 1H), 7.340-7.300 (m, 1H), 7.143 (br s, 1H), 7.040 (d, 1H), 6.504 (s, 1H), 6.360 (s, 1H), 4.492 (s, 4H), 2.365 (s, 3H), 1.920 (s, 3H).

後処理

  1. customsealed tube
  2. custompurged
  3. temperaturemaintained with an inert atmosphere of nitrogen
  4. customThe final reaction mixture
  5. customwas irradiated with microwave radiation for 2 h at 70° C
  6. washThe resulting mixture was washed with 1×100 mL of water and 2×100 mL of CH3CN
  7. filtrationThe solids were collected by filtration
  8. customThe residue was further purified by Chiral-Prep-HPLC with the following conditions (2#-Gilson Gx 281(HPLC-09): Column, Chiralpak IA2*25 cm, 5 um Chiral-P(IA)004IA00CJ-MB003
  9. customThis resulted in 34.2 mg (9%) of 9-[(S)-3-Hydroxy-3-(5-methyl-isoxazol-3-yl)-but-1-ynyl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a off-white solid LC-MS (ES, m/z)

出典と根拠

ORDレコード
ord-613e6a877468461ca8672abf2787b4cb
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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