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Triethylamine → 5-[(1R)-1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide

HRID 1913480
ノート
印刷プレビュー

反応式

HRID 1913480 の反応式
Cl.Cl.[CH2:3]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:5][N:4]1[C@H:12]1[C:20]2[C:15](=[CH:16][C:17]([C:21]3[N:22]=[CH:23][C:24]([C:27]([NH2:29])=[O:28])=[N:25][CH:26]=3)=[CH:18][CH:19]=2)[CH2:14][CH2:13]1.[CH3:30][O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][C:39](O)=[O:40])=[N:36][CH:37]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH3:30][O:31][C:32]1[CH:33]=[CH:34][C:35]([CH2:38][C:39]([N:9]2[CH2:10][CH2:11][C:6]3([CH2:5][N:4]([C@H:12]4[C:20]5[C:15](=[CH:16][C:17]([C:21]6[N:22]=[CH:23][C:24]([C:27]([NH2:29])=[O:28])=[N:25][CH:26]=6)=[CH:18][CH:19]=5)[CH2:14][CH2:13]4)[CH2:3]3)[CH2:7][CH2:8]2)=[O:40])=[N:36][CH:37]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 584384902-(5-Methoxypyridin-2-yl)acetic acidHCID 866577265-[(R)-1-(2,7-Diaza-spiro[3.5]non-2-yl)-indan-5-yl]-pyrazine-2-carboxylic acid amide dihydrochloride

生成物 1

HCID 58438488
5-[(1R)-1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide
収率 29.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 5-[(R)-1-(2,7-diaza-spiro[3.5]non-2-yl)-indan-5-yl]-pyrazine-2-carboxylic acid amide (10-1c, 28 mg, 0.08 mmol) in 3 mL of DMF was added (5-methoxy-pyridin-2-yl)-acetic acid (SM-1aa, 13.0 mg, 0.08 mmol), HBTU (33.0 mg, 0.09 mmol) and triethylamine (0.06 mL, 0.46 mmol). The solution was stirred at room temperature overnight. The reaction was concentrated under reduced pressure and coevaporated with toluene. The residue was partitioned between 10 mL of dichloromethane and 10 mL of 1N NaOH solution. The organic layer was washed with saturated brine, dried over Na2SO4 and concentrated. The crude product was purified by Biotage reverse phase column chromatography (Biotage, Inc.) using 100-60% water in acetonitrile to give the desired product 12.0 mg (27%). MS (ES+) 513.4 (M+H)+. 1H NMR (CD3OD) δ 1.56-1.81 (m, 4H), 1.81-2.09 (m, 1H), 2.11-2.35 (m, 1H), 2.93 (d, 1H), 3.12 (d, 1H), 3.20-3.27 (m, 2H), 3.31-3.41 (m, 1H), 3.43-3.66 (m, 4H), 3.69-3.89 (m, 5H), 4.06 (dd, 1H), 4.54-4.81 (m, 2H), 7.25 (d, 1H), 7.34 (dd, 1H), 7.50 (d, 1H), 7.97 (dd, 1H), 8.04 (s, 1H), 8.13 (d, 1H), 9.12 (d, 1H), 9.22 (d, 1H).

後処理

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customThe residue was partitioned between 10 mL of dichloromethane and 10 mL of 1N NaOH solution
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified by Biotage reverse phase column chromatography (Biotage, Inc.)

出典と根拠

ORDレコード
ord-f2941ead5d6f432ca699a2544759d4b3
出典データセット
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08609680B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート