Cesium carbonate → {3,5-Dichloro-4-[4-(6-methylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-phenyl}-carbamic acid tert-butyl ester

HRID 2366247Notes

Reaction equation

HRID 2366247 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18](Cl)=[N:19][CH:20]=[CH:21][C:22]=3[N:23]=2)=[C:10]([Cl:25])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[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]>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18]([NH:34][C:30]4[CH:29]=[C:28]([CH3:27])[N:33]=[CH:32][N:31]=4)=[N:19][CH:20]=[CH:21][C:22]=3[N:23]=2)=[C:10]([Cl:25])[CH:9]=1)([CH3:3])([CH3:4])[CH3:2]

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 86669003[3,5-Dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl ester

Product 1

HCID 68155873{3,5-Dichloro-4-[4-(6-methylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-phenyl}-carbamic acid tert-butyl esterYield 68%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
85 °C

Procedure

A mixture of [3,5-dichloro-4-(4-chlorothiazolo[5,4-c]pyridin-2-yl)-phenyl]-carbamic acid tert-butyl ester (0.30 g, 0.697 mmol), 6-methylpyrimidin-4-ylamine (0.073 g, 0.77 mmol), XantPhos (0.040 g, 0.0696 mmol) and Cs2CO3 (0.454 g, 1.39 mmol) in dioxane (10 mL) was degassed with a stream of argon. Pd2(dba)3 (0.032 g, 0.035 mmol) was added and the reaction mixture was heated at 85° C. for 18 hours. After cooling to room temperature, the crude reaction mixture was filtered through Celite® washing with EtOAc and the filtrate was concentrated under reduced pressure. The resultant residue was purified by column chromatography on silica gel eluting with 0-30% EtOAc in petroleum ether to afford the title compound as a yellow solid (0.238 g, 68% yield). LCMS (Method D): RT=3.14 min, m/z: 503 [M+H+].

Workup

  1. customwas degassed with a stream of argon
  2. temperatureAfter cooling to room temperature
  3. customthe crude reaction mixture
  4. filtrationwas filtered through Celite®
  5. washwashing with EtOAc
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-30% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-246f509b51694ef3a1a8916737cf073d
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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