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

HRID 595460

반응식

HRID 595460 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

반응 조건

온도
115 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d62d0717055144049fdb26eb39c9507f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242976B2

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