Cesium carbonate → HCID 66801482, compound

HRID 2366312Notes

Reaction equation

HRID 2366312 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:19]C(=O)OC(C)(C)C)[CH:5]=[C:6]([F:18])[C:7]=1[C:8]1[S:9][C:10]2[C:11](Cl)=[N:12][CH:13]=[CH:14][C:15]=2[N:16]=1.[CH3:27][C:28]1[N:33]=[CH:32][N:31]=[C:30]([NH2:34])[CH:29]=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.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]>[NH2:19][C:4]1[CH:5]=[C:6]([F:18])[C:7]([C:8]2[S:9][C:10]3[C:11]([NH:34][C:30]4[CH:29]=[C:28]([CH3:27])[N:33]=[CH:32][N:31]=4)=[N:12][CH:13]=[CH:14][C:15]=3[N:16]=2)=[C:2]([Cl:1])[CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5728526-Methylpyrimidin-4-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86669027HCID 86669027, compound

Product 1

HCID 66801482HCID 66801482, compoundYield 10.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
150 °C

Procedure

A mixture of tert-butyl N-[3-chloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-5-fluoro-phenyl]carbamate (56 mg, 0.135 mmol), 6-methylpyrimidin-4-amine (44 mg, 0.40 mmol), Pd2(dba)3 (6.2 mg, 0.00676 mmol), XantPhos (7.8 mg, 0.0135 mmol) and Cs2CO3 (88 mg, 0.27 mmol) in 1,4-Dioxane (2 mL) was heated at 150° C. in a microwave reactor for 20 min, The mixture was filtered through Celite, washed with EtOAc, concentrated. The crude product was purified by reverse phase HPLC to give the title compound (5.4 mg, 10% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.48 (s, 1H), 8.61 (s, 1H), 8.39 (d, J=5.6 Hz, 1H), 7.75 (d, J=5.6 Hz, 1H), 7.58 (s, 1H), 6.66 (s, 1H), 6.49 (dd, J=12.7, 2.0 Hz, 1H), 6.34 (s, 2H), 2.38 (s, 3H). LCMS (Method B): RT=3.43 min, m/z 387.0 [M+H+].

Workup

  1. filtrationThe mixture was filtered through Celite
  2. washwashed with EtOAc
  3. concentrationconcentrated
  4. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-cebf736865644a6a9304e472251c445f
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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