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

HRID 1530584
ノート
印刷プレビュー

反応式

HRID 1530584 の反応式
[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([S:23][CH:24]5[CH2:29][CH2:28][N:27]([C:30]([CH3:35])([CH3:34])[C:31]([OH:33])=O)[CH2:26][CH2:25]5)=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].CC[N:38](C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.N.CCN=C=NCCCN(C)C>CN(C=O)C>[CH:1]([N:4]1[C:8]([C:9]2[N:18]=[C:17]3[N:11]([CH2:12][CH2:13][O:14][C:15]4[CH:22]=[CH:21][C:20]([S:23][CH:24]5[CH2:29][CH2:28][N:27]([C:30]([CH3:34])([CH3:35])[C:31]([NH2:38])=[O:33])[CH2:26][CH2:25]5)=[CH:19][C:16]=43)[CH:10]=2)=[N:7][CH:6]=[N:5]1)([CH3:2])[CH3:3]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 222AmmoniaHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 683131542-{4-[2-(2-Isopropyl-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 68313144
2-{4-[2-(2-Isopropyl-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 78.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a suspension of 2-{4-[2-(2-isopropyl-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 (20 mg, 0.0411 mmol) in DMF (1.5 mL) was added DIPEA (21 ul, 0.123 mmol), HOBt.NH3 (9 mg, 0.0616 mmol) and EDCI (12 mg, 0.0616 mmol) and the reaction mixture was stirred at RT for 18 h. The mixture was then partitioned between EtOAc and water. The aqueous layer was further extracted with EtOAc and 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 2-8% 2M NH3/MeOH in DCM) affording 2-{4-[2-(2-Isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulen-9-ylsulfanyl]piperidin-1-yl}isobutyramide as a colorless gum (16 mg, 77%). LCMS: RT 2.16/2.19 min [M+H]+ 496.1

後処理

  1. customThe mixture was then partitioned between EtOAc and water
  2. extractionThe aqueous layer was further extracted with EtOAc
  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 2-8% 2M NH3/MeOH in DCM)

出典と根拠

ORDレコード
ord-e0b579a378704fc6ac5bf4be9733f4c5
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09090628B2

反応ノート

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