1,2-Dichloroethane → HCID 89930823, compound

HRID 527736Notes

Reaction equation

HRID 527736 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=O)[CH2:11][Si:10]([CH3:17])([CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.N1C2C(=NC=CC=2)N(O)N=1.[C@H:32]1([NH2:42])[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:35][CH2:34][CH2:33]1.CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.[Cl-].[Na+].O>[CH3:16][Si:10]1([CH3:17])[CH2:11][C@@H:12]([C:13](=[O:15])[NH:42][C@H:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35][CH2:34][CH2:33]2)[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 70580721-Aminotetralin, (R)-HCID 10825193(R)-1-(tert-butoxycarbonyl)-3,3-dimethyl-1,3-azasilolidine-5-carboxylic acid

Product 1

HCID 89930823HCID 89930823, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (R)-1-(tert-butoxycarbonyl)-3,3-dimethyl-1,3-azasilolidine-5-carboxylic acid (1.0 g, 3.9 mmol) in DMF (9 mL) at 0° C. was added EDC (1.3 g, 6.6 mmol) and 3H-[1,2,3]-triazolo[4,5-b]pyridin-3-ol (0.53 g, 3.9 mmol). The resulting mixture was stirred for 5 minutes and treated with a solution of (R)-1,2,3,4-tetrahydronaphthalen-1-amine (Alfa Aesar, 0.60 g, 4.1 mmol) in DMF (4 mL) and then DIEA (0.94 mL, 5.4 mmol). The reaction mixture was stirred at rt for 1.5 h and diluted with ethyl acetate and brine. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash column chromatography on SiO2 (eluting with 20% EtOAc/hexane) to afford the title compound (1.25 g, 83%). 1H NMR (400 MHz, CDCl3) δ 7.22-7.02 (m, 4H), 5.22-4.61 (m, 2H), 3.16-2.65 (m, 3H), 2.52 (d, J=14.5 Hz, 1H), 2.12-1.95 (m, 1H), 1.88-1.76 (m, 3H), 1.52-1.28 (m, 11H), 0.43-0.16 (m, 6H); MS(ESI+) m/z 389.4 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at rt for 1.5 h
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on SiO2 (eluting with 20% EtOAc/hexane)

Sources & evidence

ORD record
ord-ddcc6154f9854fbf8ca0e33b2309c9bb
Source dataset
uspto-grants-2016_05
Patent number
US09345740B2

Reaction notes

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