Triethylamine → 7-[(5-Methoxypyridin-2-yl)acetyl]-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane

HRID 1913450Notes

Reaction equation

HRID 1913450 reaction equation
Cl.Cl.[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([N:14]2[CH2:22][CH2:21][C:17]3([CH2:20][NH:19][CH2:18]3)[CH2:16][CH2:15]2)=[O:13])=[N:9][CH:10]=1.[CH3:23][C:24]1([CH3:41])[C:28]([CH3:30])([CH3:29])[O:27][B:26]([C:31]2[CH:32]=[C:33]3[C:37](=[CH:38][CH:39]=2)[C:36](=O)[CH2:35][CH2:34]3)[O:25]1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([N:14]2[CH2:15][CH2:16][C:17]3([CH2:20][N:19]([CH:36]4[C:37]5[C:33](=[CH:32][C:31]([B:26]6[O:27][C:28]([CH3:30])([CH3:29])[C:24]([CH3:41])([CH3:23])[O:25]6)=[CH:39][CH:38]=5)[CH2:34][CH2:35]4)[CH2:18]3)[CH2:21][CH2:22]2)=[O:13])=[N:9][CH:10]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-oneHCID 674075527-[(5-Methoxypyridin-2-yl)acetyl]-2,7-diazaspiro-[3.5]nonane dihydrochloride

Product 1

HCID 584385027-[(5-Methoxypyridin-2-yl)acetyl]-2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 63651,1-DichloroethaneSolvent

Procedure

7-[(5-Methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane dihydrochloride (2-1b, 1.8 g, 5.2 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 2.0 g, 7.75 mmol) were dissolved in anhydrous dichloroethane (50 mL). Triethylamine (2.88 mL, 20.6 mmol) was added to the solution followed by titanium(IV) isopropoxide (3.06 mL, 2.09 g) and the reaction mixture was stirred at ambient temperature for 1 hour. Sodium triacetoxyborohydride (4.38 g, 20.7 mmol) was added and the reaction was stirred at room temperature for 15 hours. The reaction was quenched by the addition of 20 mL saturated sodium bicarbonate. The aqueous solution was washed with 100 mL of dichloromethane and the organic solution was washed with brine and dried over anhydrous Na2SO4. Removal of the solvent under vacuum afforded the crude product (4.0 g) as a brown foam. The crude product was purified by silica chromatography on an Analogix system (Analogix Inc., Burlington, Wis.), eluting with 1-10% MeOH in CH2Cl2 to give the title compound (2-1c) as a brown paste (1.1 g, 41%). MS (ES+) 518.6 (M+H)+. 1H NMR (CDCl3) δ1.27 (s, 12H), 1.50-1.65 (m, 4H), 1.76-1.85 (m, 1H), 1.99-2.10 (m, 1H), 2.64-2.76 (m, 1H), 2.90-2.98 (m, 1H), 3.00-3.13 (m, 4H), 3.42 (d, 4H), 3.77 (s, 3H), 3.80 (s, 2H), 3.85 (s, 1H), 7.08-7.12 (m, 1H), 7.18-7.22 (m, 2H), 7.54-7.58 (m, 1H), 7.63 (s, 1H), 8.14-8.16 (m, 1H).

Workup

  1. stirringthe reaction was stirred at room temperature for 15 hours
  2. customThe reaction was quenched by the addition of 20 mL saturated sodium bicarbonate
  3. washThe aqueous solution was washed with 100 mL of dichloromethane
  4. washthe organic solution was washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customRemoval of the solvent under vacuum
  7. customafforded the crude product (4.0 g) as a brown foam
  8. customThe crude product was purified by silica chromatography on an Analogix system (Analogix Inc., Burlington, Wis.)
  9. washeluting with 1-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-3cf95cd962f94754980fea555d4db339
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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