Cesium carbonate → Ethyl 4-amino-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

HRID 573601Notes

Reaction equation

HRID 573601 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15](Br)=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[C:3]=12.[C:26](=[O:33])([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[NH2:27].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].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>[NH2:1][C:2]1[C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:6]([CH3:13])[N:5]=[C:4]2[S:14][C:15]([NH:27][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:33])=[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[C:3]=12

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 68324129Ethyl 4-amino-2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68380693Ethyl 4-amino-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylateYield 93.2%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of ethyl 4-amino-2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridine-5-carboxylate (Description 15) (1.52 g, 3.61 mmol), tert-butyl carbamate (0.845 g, 7.22 mmol), Pd2(dba)3 (0.066 g, 0.072 mmol), xantphos (0.084 g, 0.144 mmol) and Cs2CO3 (3.53 g, 10.82 mmol) in 1,4-dioxane (25 mL) was heated at 110° C. for ca. 6 h. After cooling to RT, the mixture was filtered through celite and the filtrate was concentrated. The residue was purified by chromatography, eluting with a gradient of 30-60% ethyl acetate in cyclohexane, to give the title compound (1.54 g). LCMS (A) m/z: 458 [M+1]+, Rt 1.44 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe mixture was filtered through celite
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by chromatography
  5. washeluting with a gradient of 30-60% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-7c30b6a23af04ae685251a701bc9edd3
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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