Cesium carbonate → HCID 66802090, compound

HRID 2366294Notes

Reaction equation

HRID 2366294 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:12]=3[C:13]#[N:14])=[N:10][C:6]=2[C:5]([F:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[N:27]=[CH:26][N:25]=[C:24]([CH2:28][OH:29])[CH:23]=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.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.O.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:19][C:18]1[C:11]([C:9]2[S:8][C:7]3[C:2]([NH:21][C:22]4[CH:23]=[C:24]([CH2:28][OH:29])[N:25]=[CH:26][N:27]=4)=[N:3][CH:4]=[C:5]([F:20])[C:6]=3[N:10]=2)=[C:12]([CH:15]=[CH:16][CH:17]=1)[C:13]#[N:14]

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934615(6-Aminopyrimidin-4-yl)methanolHCID 86669020HCID 86669020, compound

Product 1

HCID 66802090HCID 66802090, compoundYield 52%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(4-bromo-7-fluorothiazolo[5,4-c]pyridin-2-yl)-3-chlorobenzonitrile (0.35 g, 0.95 mmol), (6-aminopyrimidin-4-yl)methanol (125 mg, 1.0 mmol), XantPhos (0.055 g, 0.095 mmol) and Cs2CO3 (780 mg, 2.38 mmol) in dioxane (11 mL) was degassed with a stream of argon. Pd2(dba)3 (0.048 g, 0.047 mmol) was added and the reaction mixture was heated at 80° C. for 6 hours in a sealed vial. After cooling to room temperature, the crude reaction mixture was diluted with EtOAc (100 mL) and water (20 mL) and the resultant mixture was filtered through Celite® washing with EtOAc (50 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated under reduced pressure The resultant residue was purified by column chromatography on silica gel eluting with 0-10% MeOH in DCM, then triturated with diethyl ether (×2), to afford the title compound as a pale yellow solid (203 mg, 52% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.79 (br s, 1H), 8.61 (d, J=1.2 Hz, 1H), 8.52 (d, J=1.8 Hz, 1H), 8.16-8.08 (m, 2H), 7.86 (t, J=8.0 Hz, 1H), 7.58 (s, 1H), 5.57 (t, J=5.7 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H). LCMS (Method C): RT=3.29 min, m/z: 413 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. customthe crude reaction mixture
  4. filtrationthe resultant mixture was filtered through Celite®
  5. washwashing with EtOAc (50 mL)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure The resultant residue
  9. customwas purified by column chromatography on silica gel eluting with 0-10% MeOH in DCM
  10. customtriturated with diethyl ether (×2)

Sources & evidence

ORD record
ord-41610d0213cd4e2394b2421c099b65c1
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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