Cesium carbonate → [2-(2,6-Dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amine

HRID 2366255Notes

Reaction equation

HRID 2366255 reaction equation
Cl[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][C:14]([CH:18]4[CH2:20][CH2:19]4)=[CH:13][C:12]=3[Cl:21])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH3:22][C:23]1[N:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=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]>[Cl:17][C:16]1[CH:15]=[C:14]([CH:18]2[CH2:19][CH2:20]2)[CH:13]=[C:12]([Cl:21])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:29][C:25]3[CH:24]=[C:23]([CH3:22])[N:28]=[CH:27][N:26]=3)=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=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 867233174-Chloro-2-(2,6-dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridine

Product 1

HCID 66801628[2-(2,6-Dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridin-4-yl]-(6-methylpyrimidin-4-yl)-amineYield 4%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 4-chloro-2-(2,6-dichloro-4-cyclopropylphenyl)thiazolo[5,4-c]pyridine (0.148 g, 0.416 mmol), 6-methylpyrimidin-4-ylamine (0.044 g, 0.458 mmol), XantPhos (0.024 g, 0.0416 mmol), Cs2CO3 (0.271 g, 0.832 mmol) and Pd2(dba)3 (0.019 g, 0.021 mmol) in dioxane (1 mL) was degassed with a stream of argon and was then irradiated at 150° C. for 0.5 hour in a microwave reactor. After cooling to room temperature, the crude reaction mixture was filtered through Celite® washing with DCM and the filtrate was concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-2% MeOH in DCM followed by reverse phase HPLC (Phenomenex Gemini 5 μm C18 on a 30 minute gradient 50-90%, 0.1% HCO2H in MeOH/H2O) to afford the title compound (7 mg, 4% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.63 (s, 1H), 8.63 (d, J=1.2 Hz, 1H), 8.45 (d, J=5.6 Hz, 1H), 7.82 (d, J=5.6 Hz, 1H), 7.62 (s, 1H), 7.45 (s, 2H), 2.40 (s, 3H), 2.14-2.05 (m, 1H), 1.13-1.07 (m, 2H), 0.94-0.89 (m, 2H). LCMS (Method C): RT=4.17 min, m/z: 428 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. customwas then irradiated at 150° C. for 0.5 hour in a microwave reactor
  3. customthe crude reaction mixture
  4. filtrationwas filtered through Celite®
  5. washwashing with DCM
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-2% MeOH in DCM
  8. customC18 on a 30 minute gradient 50-90%, 0.1% HCO2H in MeOH/H2O

Sources & evidence

ORD record
ord-32105010b6204f9690425bf4c05673c4
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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