Sodium Carbonate → Ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate

HRID 877527Notes

Reaction equation

HRID 877527 reaction equation
Cl[C:2]1[CH:12]=[C:11]([NH:13][CH:14]2[CH2:17]C[CH2:15]2)[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:27]=[CH:26][C:22]2[N:23]=[CH:24][S:25][C:21]=2[CH:20]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[S:25]1[C:21]2[CH:20]=[C:19]([NH:18][C:2]3[CH:12]=[C:11]([NH:13][CH:14]([CH3:15])[CH3:17])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][N:3]=3)[CH:27]=[CH:26][C:22]=2[N:23]=[CH:24]1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 682886-AminobenzothiazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 89689654Ethyl 6-chloro-4-(cyclobutylamino)nicotinate

Product 1

HCID 89689730Ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of ethyl 6-chloro-4-(isopropylamino)nicotinate (2) (5 g, 20.66 mmol) in dioxane (30 mL): H2O (5 mL), 6-amino benzothiazole (20.66 mmol, 1 equiv.), xanthphos (8.2 mmol, 0.4 equiv.) and Na2CO3 (82.6 mmol, 4 equiv.) were added and degassed for 10 min. To the reaction mixture Pd2(dba)3 (8.2 mmol, 0.4 equiv.) was added and degassed again for 10 min. It was then heated at 115° C., overnight. The reaction was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel and EtOAC: pet. Ether as eluent to afford ethyl 6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)nicotinate (3). LC/MS: Acquity BEH C18 2.1×50 mm, 1.8 micron; Solvent A=0.1% TFA in water; Solvent B=0.1% TFA in ACN; gradient 0-100% B over 2 min; retention time: 0.78 min; LCMS (ES-API), m/z 357.8 (M+H).

Workup

  1. customdegassed for 10 min
  2. customdegassed again for 10 min
  3. temperatureThe reaction was cooled
  4. filtrationfiltered through small pad of celite
  5. customThe filtrate obtained
  6. concentrationwas concentrated
  7. customto provide crude material
  8. customThe crude material was purified by column chromatography through silica gel and EtOAC

Sources & evidence

ORD record
ord-4be1aed0c9d84924a059eba6573f32aa
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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