Tetrahydrofuran → HCID 44125204, compound

HRID 2040982Notes

Reaction equation

HRID 2040982 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1CCCC1.Cl[C:40]1[N:45]=[CH:44][C:43]([C:46]([NH:48][CH3:49])=[O:47])=[CH:42][CH:41]=1>CN(C)C=O>[CH3:49][NH:48][C:46](=[O:47])[C:43]1[CH:42]=[CH:41][C:40]([O:21][C:19]2[CH:18]=[CH:17][C:15]3[N:16]=[C:12]([N:9]4[CH2:10][CH2:11][C@@H:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:8]4)[S:13][C:14]=3[CH:20]=2)=[N:45][CH:44]=1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 123642306-Chloro-N-methylnicotinamideHCID 44124594HCID 44124594, compound

Product 1

HCID 44125204HCID 44125204, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-ol (Example 47) in N,N-dimethylformamide (˜0.06 M) under a dry nitrogen atmosphere is placed in a microwave vial and stirred. Sodium hydride or a 1 M solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran (1.2 equivalents) is added to the reaction mixture and stirring is continued for 45 minutes. 6-Chloro-N-methyl-3-pyridinecarboxamide (CAS#54189-82-1, 1.2 equivalents) is added to the reaction mixture and stirring is continued for 2-3 hours at 100° C. under microwave irradiation with the cooling air remaining on for the duration of the heating cycle. The reaction mixture is cooled to ambient temperature, dried (MgSO4), and filtered. The filtrate is concentrated under reduced pressure and the residue is purified by column chromatography on silica gel, eluting with 98:2 dichloromethane/2 M NH3 in methanol. Fractions containing product are combined and concentrated under reduced pressure to give (R)—N-methyl-6-(2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-yloxy)nicotinamide.

Workup

  1. stirringstirring
  2. stirringstirring
  3. customis continued for 2-3 hours at 100° C. under microwave irradiation with the cooling air
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationThe filtrate is concentrated under reduced pressure
  7. customthe residue is purified by column chromatography on silica gel
  8. washeluting with 98:2 dichloromethane/2 M NH3 in methanol
  9. additionFractions containing product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b09045fe34994ae8a8bb3f24d52743af
Source dataset
uspto-grants-2013_11
Patent number
US08580968B2

Reaction notes

Loading…