Triethylamine → 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane

HRID 1913478ノート

反応式

HRID 1913478 の反応式
[N:1]1[N:2]([C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[C@H:11]([N:15]2[CH2:18][C:17]4([CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[CH2:16]2)[CH2:10][CH2:9]3)[N:3]=[CH:4][CH:5]=1.[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][C:32](O)=[O:33])=[N:29][CH:30]=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C>CN(C)C=O.CN(C1C=CN=CC=1)C>[CH3:24][C:25]1[CH:26]=[CH:27][C:28]([CH2:31][C:32]([N:21]2[CH2:22][CH2:23][C:17]3([CH2:16][N:15]([CH:11]4[C:12]5[C:8](=[CH:7][C:6]([N:2]6[N:3]=[CH:4][CH:5]=[N:1]6)=[CH:14][CH:13]=5)[CH2:9][CH2:10]4)[CH2:18]3)[CH2:19][CH2:20]2)=[O:33])=[N:29][CH:30]=1

参加物

7

反応物 4

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 190662662-(5-Methylpyridin-2-yl)acetic acidHCID 584384932-((R)-5-[1,2,3]triazol-2-yl-indan-1-yl)-2,7-diaza-spiro[3.5]nonane

生成物 1

HCID 533901807-[(5-methylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane収率 72.4%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-((R)-5-[1,2,3]triazol-2-yl-indan-1-yl)-2,7-diaza-spiro[3.5]nonane (6-1c, 200 mg, 0.65 mmol) in 3 mL of dimethylformamide was added (5-methyl-pyridin-2-yl)-acetic acid (SM-1ab, 98 mg, 0.65 mmol), triethylamine (131 mg, 1.29 mmol), EDCI (130 mg, 0.68 mmol) and a catalytic amount of DMAP. The mixture was stirred at room temperature overnight. The reaction mixture was quenched by the addition of 10 mL of saturated NaHCO3 and diluted with 50 mL of dichloromethane. The organic layer was washed with saturated brine, dried over Na2SO4 and concentrated. The crude product was purified on Analogix (Analogix Inc., Burlington, Wis.) 4 g silica column (0-20% MeOH in ethyl acetate (1% triethyl amine)) to provide the title compound (207 mg, 72.4%) as a brown gum. MS (ES+) 443.4 (M+H)+. 1H NMR (CD3OD) δ 1.58-1.79 (m, 4H), 1.94-2.16 (m, 2H), 2.20-2.31 (m, 2H), 2.31 (s, 3H), 2.78-2.98 (m, 1H), 3.09-3.16 (m, 1H), 3.17-3.32 (m, 2H), 3.38-3.57 (m, 4H), 3.88 (s, 2H), 3.99-4.20 (m, 1H), 7.21 (d, 1H), 7.39-7.51 (m, 2H), 7.80 (d, 2H), 7.89-7.94 (m, 1H), 7.97 (s, 1H), 8.24-8.38 (m, 1H). [α]D20=+47.2 deg (c=9.4 mg/mL, methanol).

後処理

  1. customThe reaction mixture was quenched by the addition of 10 mL of saturated NaHCO3
  2. additiondiluted with 50 mL of dichloromethane
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude product was purified on Analogix (Analogix Inc., Burlington, Wis.) 4 g silica column (0-20% MeOH in ethyl acetate (1% triethyl amine))

出典と根拠

ORDレコード
ord-672fc1578c1f47adb043bcac1eb81aae
出典データセット
uspto-grants-2013_12
特許番号
US08609680B2

反応ノート

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