p-Fluoronitrobenzene → HCID 71483887, compound

HRID 2409932Notes

Reaction equation

HRID 2409932 reaction equation
[CH:1]12[NH:8][C@H:5]([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH:2]2[NH:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[NH:16][C:17]1[O:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)=[CH:20][N:21]=1.F[C:34]1[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][CH:35]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N+:40]([C:37]1[CH:38]=[CH:39][C:34]([N:8]2[CH2:5][CH:4]3[CH2:6][CH2:7][CH:1]2[C@@H:2]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]2[NH:16][C:17]2[O:18][C:19]([C:22]4[CH:23]=[CH:24][C:25]([O:28][C:29]([F:31])([F:30])[F:32])=[CH:26][CH:27]=4)=[CH:20][N:21]=2)[CH2:3]3)=[CH:35][CH:36]=1)([O-:42])=[O:41]

Participants

5

Reactant 3

HCID 9590p-FluoronitrobenzeneHCID 11430Potassium CarbonateHCID 86690352HCID 86690352, compound

Product 1

HCID 71483887HCID 71483887, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (1R,2R)—N1-((5R)-8-azabicyclo[3.2.1]octan-2-yl)-N2-(5-(4-(trifluoromethoxy)phenyl)oxazol-2-yl)cyclohexane-1,2-diamine (28 mg, 0.062 mmol) and 4-fluoronitrobenzene (9.65 mg, 0.069 mmol) in DMF (0.38 ml) was added K2CO3. The reaction mixture was then heated at 80° C. for 4 hrs. The reaction mixture was partitioned between EtOAc and water. The organic phase was separated, dried over MgSO4, filtered and concentrated. The residue was purified by RP prep-HPLC using method A with two isomers were separating. The fractions with the desired product, which eluted later than the undesired isomer, were concentrated to give (1R,2R)—N1-((6S)-2-(4-nitrophenyl)-2-azabicyclo[2.2.2]octan-6-yl)-N2-(5-(4-(trifluoromethoxy)phenyl)oxazol-2-yl)cyclohexane-1,2-diamine (5.82 mg, 0.0102 mmol, 16.4% yield) as a yellow solid. Anal. Calcd. for C29H32F3N5O4 m/z 571.2, found: 572.2 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 11.04 (1 H, br. s.), 7.88 (2 H, d, J=9.3 Hz), 7.55 (2 H, d, J=8.2 Hz), 7.30 (2 H, d, J=8.2 Hz), 7.02 (1 H, s), 6.78 (2 H, d, J=9.3 Hz), 6.38 (1 H, br. s.), 4.65 (1 H, d, J=6.0 Hz), 4.36 (1 H, d, J=6.0 Hz), 4.33-4.20 (1 H, m), 3.80-3.73 (1 H, m), 3.40-3.27 (1 H, m), 2.26-1.65 (13 H, m), 1.65-1.30 (3 H, m).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. customThe organic phase was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by RP
  7. customwere separating
  8. washThe fractions with the desired product, which eluted later than the undesired isomer
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-79b00ae9752f4fe4a529a08d771bd339
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

Loading…