HCID 178425096, compound → HCID 178425095, compound

HRID 2045094Notes

Reaction equation

HRID 2045094 reaction equation
[C:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([CH2:10][O:11][C:12]2[N:17]=[CH:16][C:15]([S:18]([NH:21][C:22](=[O:61])[C:23]3[CH:28]=[CH:27][C:26]([N:29]4[CH2:34][CH2:33][N:32]([CH2:35][C:36]5[CH2:41][CH2:40][C:39]([CH3:43])([CH3:42])[CH2:38][C:37]=5[C:44]5[CH:49]=[CH:48][C:47]([Cl:50])=[CH:46][CH:45]=5)[CH2:31][CH2:30]4)=[CH:25][C:24]=3[O:51][C:52]3[CH:60]=[CH:59][CH:58]=[C:57]4[C:53]=3[CH:54]=[N:55][NH:56]4)(=[O:20])=[O:19])=[CH:14][C:13]=2[Cl:62])[CH2:6][CH2:5]1)(=O)[NH2:2]>O1CCOCC1.N1C=CC=CC=1>[Cl:62][C:13]1[CH:14]=[C:15]([S:18]([NH:21][C:22](=[O:61])[C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:30][CH2:31][N:32]([CH2:35][C:36]4[CH2:41][CH2:40][C:39]([CH3:43])([CH3:42])[CH2:38][C:37]=4[C:44]4[CH:45]=[CH:46][C:47]([Cl:50])=[CH:48][CH:49]=4)[CH2:33][CH2:34]3)=[CH:25][C:24]=2[O:51][C:52]2[CH:60]=[CH:59][CH:58]=[C:57]3[C:53]=2[CH:54]=[N:55][NH:56]3)(=[O:20])=[O:19])[CH:16]=[N:17][C:12]=1[O:11][CH2:10][C@H:7]1[CH2:8][CH2:9][C@H:4]([C:1]#[N:2])[CH2:5][CH2:6]1

Participants

4

Reactant 1

HCID 178425096HCID 178425096, compound

Product 1

HCID 178425095HCID 178425095, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of EXAMPLE 483D (50 mg) in dioxane (12 mL) and pyridine (1.2 mL) was cooled in an ice-water bath. The mixture was slightly warmed by removing the ice bath and then trifluoroacetic acid (0.3 mL) was added. The reaction was stirred for 1 hour and quenched with methanol and aqueous NaOH. The resulting mixture was stirred for 1 hour and concentrated. The residue was purified by reverse phase HPLC, and eluted with 40%-70% acetonitrile in 0.1% trifluoroacetic acid water over 40 minutes. The desired fractions were concentrated to remove acetonitrile, neutralized with NaHCO3 and extracted with dichloromethane. The dichloromethane layer was dried over Na2SO4, filtered, concentrated and dried to provide the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ 13.10 (s, 1H), 8.27 (d, 1H), 7.85 (d, 1H), 7.80 (s, 1H), 7.58 (d, 1H), 7.37 (d, 2H), 7.02-7.11 (m, 4H), 6.80 (dd, 1H), 6.54 (d, 1H), 6.14 (d, 1H), 4.19 (d, 2H), 3.22 (s, 4H), 2.97 (s, 2H), 2.59-2.71 (m, 1H), 2.41 (s, 2H), 2.18 (s, 2H), 2.05 (dd, 2H), 1.98 (s, 2H), 1.79-1.90 (m, 3H), 1.47-1.62 (m, 2H), 1.42 (t, 2H), 1.04-1.19 (m, 2H), 0.94 (s, 6H).

Workup

  1. temperatureThe mixture was slightly warmed
  2. customby removing the ice bath
  3. additiontrifluoroacetic acid (0.3 mL) was added
  4. customquenched with methanol and aqueous NaOH
  5. stirringThe resulting mixture was stirred for 1 hour
  6. concentrationconcentrated
  7. customThe residue was purified by reverse phase HPLC
  8. washeluted with 40%-70% acetonitrile in 0.1% trifluoroacetic acid water over 40 minutes
  9. concentrationThe desired fractions were concentrated
  10. customto remove acetonitrile
  11. extractionextracted with dichloromethane
  12. dry with materialThe dichloromethane layer was dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customdried

Sources & evidence

ORD record
ord-d7ecafb21b9049dcb359f080fd4edb84
Source dataset
uspto-grants-2013_11
Patent number
US08586754B2

Reaction notes

Loading…