Isoamylamine → HCID 11382214, compound

HRID 422227Notes

Reaction equation

HRID 422227 reaction equation
O=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[CH2:21]([NH2:26])[CH2:22][CH:23]([CH3:25])[CH3:24].C1COCC1.[BH3-]C#N.[Na+]>CO.Cl[Ti](Cl)(Cl)Cl>[CH3:24][CH:23]([CH3:25])[CH2:22][CH2:21][NH:26][CH:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][N:13]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 7894IsoamylamineHCID 8028TetrahydrofuranHCID 5003444Sodium cyanoborohydrideHCID 597506396-(1-Oxo-indan-5-yloxy)-nicotinamide2×

Product 1

HCID 11382214HCID 11382214, compoundYield 48.2%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolvent

Procedure

Add Ti(iPrO)4 (1.70 g, 6.00 mmol) to a suspension of 6-(1-oxo-indan-5-yloxy)nicotinamide (Intermediate 4, 805 mg, 3.00 mmol), isoamyl amine (314 mg, 3.60 mmol) and THF (10 ml) and stir overnight under a nitrogen atmosphere at ambient temperature. Treat the reaction mixture with a solution of TiCl4 (1.0M/DCM, 6.00 ml, 6.00 mmol) and stir at ambient temperature for three hours before adding NaBH3CN (377 mg, 6.00 mmol) dissolved in MeOH (5 ml). After an additional three hours, quench the reaction with 2N aq. NaOH, making the suspension basic. Stir the suspension for one hour and filter through a filter aid to remove solids, washing them with EtOAc. Separate layers in the filtrate/wash and wash the organic layer with brine before drying (MgSO4) and concentrating. Purify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM) to obtain 491 mg of the title compound as a light yellow solid. Mass spectrum (ion spray): m/z=340 (M+1); 1HNMR (CDCl3): 8.59 (s, 1H), 8.16 (d, 1H), 7.39 (d, 1H), 7.00 (s, 1H), 6.97-6.94 (m, 2H), 5.87 (br. s, 2H), 4.25 (t, 1H), 3.02 (m, 1H), 2.83 (m, 1H), 2.75 (t 2H), 2.46 (m, 1H), 1.89 (m, 1H), 1.67 (m, 1H), 1.44 (m, 2H), 0.92 (d, 6H).

Workup

  1. stirringstir at ambient temperature for three hours
  2. waitAfter an additional three hours
  3. customquench
  4. customthe reaction with 2N aq. NaOH
  5. stirringStir the suspension for one hour
  6. filtrationfilter through a filter aid
  7. customto remove solids
  8. washwashing them with EtOAc
  9. washSeparate layers in the filtrate/wash
  10. washwash the organic layer with brine
  11. dry with materialbefore drying (MgSO4)
  12. concentrationconcentrating
  13. customPurify on silica gel (5% (1N NH3/MeOH)/45% EtOAc/DCM)

Sources & evidence

ORD record
ord-4cbb0186c5894092a76e8f2a05bd65be
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

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