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 1913478노트

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HRID 1913478 반응식
[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

참가 물질

7

반응물 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

생성물 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]nonane수율 72.4%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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))

출처 및 근거

ORD 기록
ord-672fc1578c1f47adb043bcac1eb81aae
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08609680B2

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