1,2-Dichloroethane → HCID 89930896, compound

HRID 527744Notes

Reaction equation

HRID 527744 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[C:25]([OH:27])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.N1C2C(=NC=CC=2)N(O)N=1.[C@H:42]1([NH2:52])[C:51]2[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH2:45][CH2:44][CH2:43]1.CN1CCOCC1>CN(C=O)C.C(OCC)(=O)C.[Cl-].[Na+].O>[CH3:24][O:23][C:21]([C:18]1[CH:17]=[CH:16][C:15]([CH2:14][O:13][C@@H:11]2[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[C@H:9]([C:25](=[O:27])[NH:52][C@H:42]3[C:51]4[C:46](=[CH:47][CH:48]=[CH:49][CH:50]=4)[CH2:45][CH2:44][CH2:43]3)[CH2:10]2)=[CH:20][CH:19]=1)=[O:22]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 181649HOAtHCID 70580721-Aminotetralin, (R)-HCID 89921997HCID 89921997, compound

Product 1

HCID 89930896HCID 89930896, compoundYield 81%

Reagents, catalysts & solvents 3

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

Procedure

To a solution of (2S,4S)-1-(tert-butoxycarbonyl)-4-((4-(methoxycarbonyl)benzyl)oxy)pyrrolidine-2-carboxylic acid (1.2 g, 3.2 mmol) in DMF (10 mL) was added EDC (0.91 g, 4.7 mmol) and 3H-[1,2,3]-triazolo[4,5-b]pyridin-3-ol (0.43 g, 3.2 mmol). The reaction mixture was stirred at rt for 5 min and treated with a solution of (R)-1,2,3,4-tetrahydronaphthalen-1-amine (0.54 g, 3.6 mmol) in DMF (5 mL) and 4-methylmorpholine (0.70 mL, 6.3 mmol). The reaction mixture was stirred at rt for 1 h and diluted with ethyl acetate and brine. The organic layer was separated and washed successively with aq. NaHCO3 solution, brine, and 1N HCl solution. The organics were dried over MgSO4 and concentrated in vacuo. The resulting residue was purified by flash chromatography (eluting with 20% EtOAc/DCM) to afford the title compound as a white solid (1.3 g, 81%). 1H NMR (CDCl3) δ 7.99 (d, J=8.4 Hz, 2H), 7.33 (d, J=6.8 Hz, 2H), 7.13-6.94 (m, 3H), 6.85-6.80 (m, 1H), 5.21-5.01 (m, 1H), 4.49-4.33 (m, 2H), 4.11 (d, J=3.1 Hz, 1H), 3.93 (s, 3H), 3.70-3.41 (m, 2H), 2.74 (d, J=3.3 Hz, 2H), 2.05 (s, 2H), 1.90-1.68 (m, 3H), 1.58 (s, 1H), 1.45 (s, 10H); MS(ESI+) m/z 509.5 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred at rt for 1 h
  2. customThe organic layer was separated
  3. washwashed successively with aq. NaHCO3 solution, brine, and 1N HCl solution
  4. dry with materialThe organics were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by flash chromatography (eluting with 20% EtOAc/DCM)

Sources & evidence

ORD record
ord-5b13cb477d9b4c94b0f47e1f854227c9
Source dataset
uspto-grants-2016_05
Patent number
US09345740B2

Reaction notes

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