Cesium carbonate → 2-(2,6-Dichlorophenyl)-N-(6-methyl-2-morpholinopyrimidin-4-yl)thiazolo[5,4-c]pyridin-4-amine

HRID 2366175Notes

Reaction equation

HRID 2366175 reaction equation
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])=[N:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH3:19][C:20]1[N:25]=[C:24]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:23]=[C:22]([NH2:32])[CH:21]=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:18][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]([Cl:17])[C:11]=1[C:9]1[S:8][C:7]2[C:2]([NH:32][C:22]3[CH:21]=[C:20]([CH3:19])[N:25]=[C:24]([N:26]4[CH2:27][CH2:28][O:29][CH2:30][CH2:31]4)[N:23]=3)=[N:3][CH:4]=[CH:5][C:6]=2[N:10]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 135378446-Methyl-2-(morpholin-4-yl)pyrimidin-4-amineHCID 862804124-Bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine

Product 1

HCID 569531092-(2,6-Dichlorophenyl)-N-(6-methyl-2-morpholinopyrimidin-4-yl)thiazolo[5,4-c]pyridin-4-amineYield 31.1%

Reagents, catalysts & solvents 2

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

Procedure

To a microwave tube was added 4-bromo-2-(2,6-dichlorophenyl)thiazolo[5,4-c]pyridine (60 mg, 0.17 mmol), 6-methyl-2-morpholinopyrimidin-4-amine (0.043 g, 0.22 mmol), Pd2(dba)3 (0.013 g, 0.017 mmol), XantPhos (0.017 g, 0.034 mmol) and Cs2CO3 (0.11 g, 0.34 mmol) in dioxane (3.0 mL). The mixture was degassed with N2 for 10 minutes and then irradiated in a microwave reactor at 160° C. for 2 hours. After cooling to room temperature the solid was removed via filtration. The filtrate was concentrated under reduced pressure and the residue was purified with reverse phase column chromatography eluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3 to give the desired product as a white solid (25 mg, 31% yield). 1H NMR (500 MHz, DMSO-d6): δ 10.31 (s, 1H), 8.44 (d, J=5.5 Hz, 1H), 7.41 (d, J=5.5 Hz, 1H), 7.44-7.28 (m, 2H), 7.68-7.67 (m, 1H), 6.40 (s, 1H), 3.55-3.54 (m, 8H), 2.21 (s, 3H). LCMS (Method A): RT=6.53 min, m/z: 473.1 [M+H+].

Workup

  1. customThe mixture was degassed with N2 for 10 minutes
  2. customirradiated in a microwave reactor at 160° C. for 2 hours
  3. customwas removed via filtration
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified with reverse phase column chromatography
  6. washeluting with a 0-60% gradient of CH3CN in 0.5% NH4HCO3

Sources & evidence

ORD record
ord-0ee62f5338744e1c84cc2f9bd2fb7318
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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