Sodium Sulfate → HCID 71233140, compound

HRID 2409896Notes

Reaction equation

HRID 2409896 reaction equation
O=[C:2]1[C@@H:7]2[CH2:8][C@@H:4]([CH2:5][N:6]2[C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=2)[CH2:3]1.[NH2:17][C@@H:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]1[NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28].[O-]S([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CC(O)=O.C(Cl)Cl>[C:13]([C:12]1[CH:15]=[CH:16][C:9]([N:6]2[CH2:5][C@H:4]3[CH2:8][C@@H:7]2[C@@H:2]([NH:17][C@@H:18]2[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]2[NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:3]3)=[CH:10][CH:11]=1)#[N:14]

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 1514390(1R,2R)-trans-N-Boc-1,2-cyclohexanediamineHCID 5049666Sodium triacetoxyborohydrideHCID 86690346HCID 86690346, compound

Product 1

HCID 71233140HCID 71233140, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a round bottom flask under argon was added 4-((1S,4R)-6-oxo-2-azabicyclo[2.2.1]heptan-2-yl)benzonitrile (272 mg, 1.282 mmol), tert-butyl (1R,2R)-2-aminocyclohexylcarbamate (330 mg, 1.538 mmol), CH2Cl2 (6.4 ml), solid anhydrous Na2SO4 (1 gm) and HOAc (1 drop). Argon was bubbled through the reaction mixture for 1 min and then the reaction was stirred under argon at rt for 1 hr. After this time, sodium triacetoxy borohydride (815 mg, 3.84 mmol) was added to the reaction which was then stirred at rt overnight. The reaction mixture was then diluted with CH2Cl2. The resulting solution was wash with saturated aqueous NaHCO3, water and saturated aqueous NaCl. The organic layer was separated, dried over MgSO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex. The fractions containing the desired product were concentrated to give tert-butyl (1R,2R)-2-((1R,4R,6S)-2-(4-cyanophenyl)-2-azabicyclo[2.2.1]heptan-6-ylamino)cyclohexylcarbamate (466 mg, 1.135 mmol, 89% yield). Anal. Calcd. for C24H34N4O2 m/z 410.5, found: 411.3 (M+H)+; 1H NMR (500 MHz, CDCl3) δ ppm 7.45 (2 H, d, J=8.8 Hz), 6.55 (2 H, d, J=8.8 Hz), 4.26 (1 H, s), 3.65 (1 H, br. s.), 3.47-3.41 (1 H, m), 3.30 (1 H, dt, J=8.8, 3.0 Hz), 3.15 (1 H, d, J=8.8 Hz), 2.98 (1 H, d, J=8.2 Hz), 2.64 (1 H, s), 2.29-2.19 (2 H, m), 2.10-2.02 (1 H, m), 2.01-1.93 (1 H, m), 1.74-1.59 (4 H, m), 1.45-1.37 (1 H, m), 1.35 (9 H, s), 1.30-1.18 (2 H, m), 1.09- -0.93 (2 H, m), 0.90 (1 H, ddd, J=12.9, 3.8, 3.6 Hz).

Workup

  1. customArgon was bubbled through the reaction mixture for 1 min
  2. stirringwas then stirred at rt overnight
  3. washThe resulting solution was wash with saturated aqueous NaHCO3, water and saturated aqueous NaCl
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified
  9. washeluting with a gradient of 0-100% EtOAc/Hex
  10. additionThe fractions containing the desired product
  11. concentrationwere concentrated

Sources & evidence

ORD record
ord-89e1b4b8047245b5b602afd240175b43
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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