Cesium carbonate → HCID 67490685, compound

HRID 1879627Notes

Reaction equation

HRID 1879627 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:31]2[C:39]3[C:34](=[C:35]([Cl:44])[CH:36]=[C:37]([C:40]([F:43])([F:42])[F:41])[CH:38]=3)[NH:33][N:32]=2)[CH:9]([C:13]2[CH:30]=[CH:29][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.[C:45]([O-])([O-])=O.[Cs+].[Cs+]>CN1C(=O)CCC1.[Na+].[Cl-]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:31]2[N:32]([CH3:45])[N:33]=[C:34]3[C:39]=2[CH:38]=[C:37]([C:40]([F:41])([F:42])[F:43])[CH:36]=[C:35]3[Cl:44])[CH:9]([C:13]2[CH:30]=[CH:29][C:16]([C:17]([NH:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 178440966HCID 178440966, compound

Product 1

HCID 67490685HCID 67490685, compound

Reagents, catalysts & solvents 2

HCID 5234Sodium ChlorideSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of the product of Step A (59 mg, 0.091 mmol) in NMP (3 mL) was added Cs2CO3 (38.5 mg, 0.118 mmol) then Mel (0.007 mL, 0.1 mmol). After being stirred at RT for one hour, the mixture was diluted with saturated NaCl (act) then extracted twice with EtOAc. The combined organic layers were dried over sodium sulfate, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-20% MeOH/DCM, then further purified by PTLC eluting with 50% EtOAc/hexanes to afford the 1-methyl regioisomer (EXAMPLE 2, Step B) as well as the title compound. The title compound was resolved to provide enantiopure material by HPLC on a ChiralPak IA (2 cm×25 cm) column eluting with 9 mL/min of 3% EtOH/n-heptane. LC1 2.83 min. (M-tBu+H)+ 606.

Workup

  1. extractionthen extracted twice with EtOAc
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by silica gel chromatography
  6. washeluting with 0-20% MeOH/DCM
  7. customfurther purified by PTLC
  8. washeluting with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-daf3934428234ec0b99aa16c6a44583d
Source dataset
uspto-grants-2012_11
Patent number
US08318667B2

Reaction notes

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