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

HRID 2366213
Notes
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Reaction equation

HRID 2366213 reaction equation
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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

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+].

Workup

  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

Sources & evidence

ORD record
ord-85da6d0da3ae4a639723af6bda1da34a
Source dataset
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08697708B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes