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 1913478Notes

Reaction equation

HRID 1913478 reaction equation
[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

Participants

7

Reactant 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

Product 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]nonaneYield 72.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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))

Sources & evidence

ORD record
ord-672fc1578c1f47adb043bcac1eb81aae
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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