Ammonia → 2-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide

HRID 1530379ノート

反応式

HRID 1530379 の反応式
[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:37])([CH3:36])[C:33]([OH:35])=O)[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:22])[CH3:21])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3.CC[N:40](C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.N.CCN=C=NCCCN(C)C>CN(C=O)C>[F:1][C:2]1[C:24]([S:25][CH:26]2[CH2:31][CH2:30][N:29]([C:32]([CH3:36])([CH3:37])[C:33]([NH2:40])=[O:35])[CH2:28][CH2:27]2)=[CH:23][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]1[N:15]([CH:20]([CH3:21])[CH3:22])[N:16]=[C:17]([CH3:19])[N:18]=1)[N:7]=3

参加物

7

反応物 5

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 683126382-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid

生成物 1

HCID 683130762-{4-[8-Fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide収率 56%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of 2-{4-[8-fluoro-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}-2-methylpropionic acid (174 mg, 0.329 mmol) in DMF (5 mL) were added DIPEA (169 l, 0.987 mmol), HOBt.NH3 (75 mg, 0.494 mmol) and EDCI (95 mg, 0.494 mmol) and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water and the aqueous phase was further extracted with EtOAc (×3). The combined organic layers were washed with water, followed by brine, then dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM) affording the title compound as a colorless sticky solid (96 mg, 56%). LCMS: RT 2.16 min [M+H]+ 527.8

後処理

  1. customThe mixture was then partitioned between EtOAc and water
  2. extractionthe aqueous phase was further extracted with EtOAc (×3)
  3. washThe combined organic layers were washed with water
  4. customdried
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 3-15% MeOH in DCM)

出典と根拠

ORDレコード
ord-0a27cf6948d046f8992011e0d0da0f77
出典データセット
uspto-grants-2015_07
特許番号
US09090628B2

反応ノート

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