Cesium carbonate → tert-butyl rel-[(3S,4S)-3-({6-cyano-5-[(4-methoxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]carbamate

HRID 1504897Notes

Reaction equation

HRID 1504897 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]2[C@@H:16]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:15][CH2:14][S:13](=[O:26])(=[O:25])[CH2:12]2)[CH:5]=[N:6][C:7]=1[C:8]#[N:9].[CH3:27][O:28][C:29]1[CH:34]=[C:33]([CH3:35])[N:32]=[C:31]([NH2:36])[CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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:8]([C:7]1[N:6]=[CH:5][C:4]([NH:10][C@H:11]2[C@@H:16]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:15][CH2:14][S:13](=[O:26])(=[O:25])[CH2:12]2)=[CH:3][C:2]=1[NH:36][C:31]1[CH:30]=[C:29]([O:28][CH3:27])[CH:34]=[C:33]([CH3:35])[N:32]=1)#[N:9]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 14480891HCID 14480891, compoundHCID 90354174tert-butyl rel-{(3S,4S)-3-[(5-bromo-6-cyanopyridin-3-yl)amino]-1,1-dioxidotetrahydro-2H-thiopyran-4-yl}carbamate

Product 1

HCID 90354236tert-butyl rel-[(3S,4S)-3-({6-cyano-5-[(4-methoxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]carbamate

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl rel-{(3S,4S)-3-[(5-bromo-6-cyanopyridin-3-yl)amino]-1,1-dioxidotetrahydro-2H-thiopyran-4-yl}carbamate (Enantiomer 1 from previous step) (50 mg, 0.11 mmol), 4-methoxy-6-methylpyridin-2-amine (16 mg, 0.11 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), cesium carbonate (91 mg, 0.28 mmol), and Xanthpos (13 mg, 0.022 mmol) was purged with argon for 5 minutes. 1,4-Dioxane (1.0 ml) was added, and the reaction mixture was purged with argon for 5 minutes, and then heated to 90° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered through CELITE, and concentrated under reduced pressure to afford tert-butyl rel-[(3S,4S)-3-({6-cyano-5-[(4-methoxy-6-methylpyridin-2-yl)amino]pyridin-3-yl}amino)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]carbamate, which was used directly in the next step without purification. MS ESI calc'd. for C23H31N6O5S [M+H]+ 503. found 503.

Workup

  1. customwas purged with argon for 5 minutes
  2. addition1,4-Dioxane (1.0 ml) was added
  3. customthe reaction mixture was purged with argon for 5 minutes
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationfiltered through CELITE
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8940bb4efafd4b9d81a2144b7993bd09
Source dataset
uspto-grants-2015_12
Patent number
US09216173B2

Reaction notes

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