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Cesium carbonate → 2-[2-(2,6-Dichloro-4-cyano-phenyl)-thiazolo[5,4-c]pyridine-4-ylamino]-isonicotinonitrile

HRID 2366213
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HRID 2366213 반응식
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][C:14]([C:15]#[N:16])=[CH:13][C:12]=3[Cl:20])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][N:29]=1)[C:25]#[N:26].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:20][C:12]1[CH:13]=[C:14]([C:15]#[N:16])[CH:17]=[C:18]([Cl:19])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:21][C:22]3[CH:23]=[C:24]([CH:27]=[CH:28][N:29]=3)[C:25]#[N:26])=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1
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참가 물질

7

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HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 70155242-AminoisonicotinonitrileHCID 866689964-(4-Bromothiazolo[5,4-c]pyridin-2-yl)-3,5-dichlorobenzonitrile

생성물 1

HCID 569532942-[2-(2,6-Dichloro-4-cyano-phenyl)-thiazolo[5,4-c]pyridine-4-ylamino]-isonicotinonitrile수율 68.7%

시약·촉매·용매 2

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

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온도
70 °C

실험 절차

Argon was bubbled through a suspension of 4-(4-bromo-thiazolo[5,4-c]pyridine-2-yl)-3,5-dichloro-benzonitrile (92 mg, 0.24 mmol), 2-amino-isonicotinonitrile (26 mg, 0.22 mmol), XantPhos (14 mg, 0.024 mmol) and cesium carbonate (195 mg, 0.6 mmol) in dioxane (2.5 ml) for 5 minutes then Pd2(dba)3 (11 mg, 0.012 mmol) was added. The reaction was heated at 70° C. for 8 hours and then cooled to room temperature. The reaction was partitioned between water (10 mL) and DCM (20 mL). The organic layer was separated, dried over Na2SO4 and concentrated to dryness under reduced pressure. The resultant residue was purified by silica gel flash chromatography eluting with 0-60% EtOAc in DCM. The resultant solid was triturated with diethyl ether, filtered, and left to air dry to give the desired compound as a yellow solid (64 mg, 63% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.74 (br s, 1H), 8.50 (dd, J=5.1, 0.9 Hz, 1H), 8.44 (d, J=5.6 Hz, 1H), 8.39 (s, 2H), 8.23 (s, 1H), 7.79 (d, J=5.6 Hz, 1H), 7.38 (dd, J=5.1, 1.4 Hz, 1H). LCMS (Method C): RT=4.70 min, m/z: 423 [M+H+].

후처리

  1. temperaturecooled to room temperature
  2. customThe reaction was partitioned between water (10 mL) and DCM (20 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness under reduced pressure
  6. customThe resultant residue was purified by silica gel flash chromatography
  7. washeluting with 0-60% EtOAc in DCM
  8. customThe resultant solid was triturated with diethyl ether
  9. filtrationfiltered
  10. waitleft to air
  11. customdry

출처 및 근거

ORD 기록
ord-85da6d0da3ae4a639723af6bda1da34a
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08697708B2

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