Cesium carbonate → N-(2-(2,6-Dichlorophenyl)thiazolo[5,4-c]pyridin-4-yl)-2-(dimethylamino)acetamide

HRID 2366185노트

반응식

HRID 2366185 반응식
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH3:19][N:20]([CH3:25])[CH2:21][C:22]([NH2:24])=[O:23].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.[Cs+].[Cs+]>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]>[Cl:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:24][C:22](=[O:23])[CH2:21][N:20]([CH3:25])[CH3:19])=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 2301162-(Dimethylamino)acetamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 862804124-Bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine

생성물 1

HCID 56953391N-(2-(2,6-Dichlorophenyl)thiazolo[5,4-c]pyridin-4-yl)-2-(dimethylamino)acetamide수율 25%

시약·촉매·용매 2

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

실험 절차

To a microwave tube was added 4-bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine (60 mg, 0.17 mmol), 2-(dimethylamino)acetamide (0.023 g, 0.22 mmol), Pd2(dba)3 (0.013 g, 0.017 mmol), XantPhos (0.017 g, 0.034 mmol) and Cs2CO3 (0.11 g, 0.34 mmol) in dioxane (3.0 mL). The mixture was degassed with N2 for 10 minutes and then irradiated in a microwave reactor at 160° C. for 2 hours. After cooling to room temperature the solid was removed via filtration. The filtrate was concentrated under reduced pressure and the residue was purified by reverse phase column chromatography, eluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3 to give the desired product as a white solid (15 mg, 25% yield). 1H NMR (500 MHz, DMSO-d6): δ 10.62 (s, 1H), 8.46 (d, J=6.0 Hz, 1H), 7.96 (d, J=6.0 Hz, 1H), 7.74-7.65 (m, 3H), 3.24 (s, 2H), 2.49 (s, 6H). LCMS (Method B): RT=6.01 min, m/z: 381.1 [M+H+].

후처리

  1. customThe mixture was degassed with N2 for 10 minutes
  2. customirradiated in a microwave reactor at 160° C. for 2 hours
  3. customwas removed via filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by reverse phase column chromatography
  6. washeluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3

출처 및 근거

ORD 기록
ord-18fb0ffe89604d1e94a2a5a822e85c14
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697708B2

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