Cesium carbonate → HCID 86700156, compound

HRID 879355Notes

Reaction equation

HRID 879355 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:31]([CH3:32])=[CH:30][C:15]2[N:16]=[C:17]([C:19]3[CH:29]=[CH:28][C:22]4[N:23]([CH3:27])[C:24](=[O:26])[NH:25][C:21]=4[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:40][N:41]1[CH2:46][CH2:45][CH:44](Br)[CH2:43][CH2:42]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.N1C=CC=CC=1>[C:1]([O:5][C@@H:6]([C:12]1[C:31]([CH3:32])=[CH:30][C:15]2[N:16]=[C:17]([C:19]3[CH:29]=[CH:28][C:22]4[N:23]([CH3:27])[C:24](=[O:26])[N:25]([CH:44]5[CH2:45][CH2:46][N:41]([CH3:40])[CH2:42][CH2:43]5)[C:21]=4[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:33]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][CH:34]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 115213614-bromo-1-methylpiperidine2×HCID 86700157HCID 86700157, compound

Product 1

HCID 86700156HCID 86700156, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)benzo[d]thiazol-6-yl)acetate (47 mg, 0.083 mmol) in DMF (1 mL), pyridine (0.5 mL), was added N-methyl-4-bromopiperidine (26 mg, 0.146 mmol). The reaction was stirred at 85° C. overnight. Then Cs2CO3 (54 mg) was added, raised temp to 100° C. and stirred overnight. More N-methyl-4-bromopiperidine (50 mg 0.28 mmol), the mixture was heated at 100° C. for 2 days. The reaction was quenched by adding water, extracted by EtOAc, dried by MgSO4, filtered, concentrated down and purified by silica gel column, first 0-100% EtOAc in hexanes to elute (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)benzo[d]thiazol-6-yl)acetate , then switched to 0-20% MeOH in DCM to elute the product. LCMS-ESI+: calc'd for C36H41ClN4O4S: 661.2 (M+H+); found: 661.3.

Workup

  1. temperatureraised temp to 100° C.
  2. stirringstirred overnight
  3. customThe reaction was quenched
  4. additionby adding water
  5. extractionextracted by EtOAc
  6. dry with materialdried by MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated down
  9. custompurified by silica gel column, first 0-100% EtOAc in hexanes
  10. washto elute (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(1-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)benzo[d]thiazol-6-yl)acetate
  11. washto elute the product

Sources & evidence

ORD record
ord-179ea47065e24849859064ac47829fd9
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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