Hexane → HCID 57504501, compound

HRID 1098145Notes

Reaction equation

HRID 1098145 reaction equation
C[Al](C)C.CCCCCC.[CH3:11][S:12][C:13]1[CH:14]=[CH:15][C:16]([NH2:19])=[N:17][CH:18]=1.[Cl:20][C:21]1[C:22]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35]([O:36][C@@H:37]([CH2:42][O:43][CH2:44][CH3:45])[C:38](OC)=[O:39])=[C:30]3[CH:29]=[N:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1>C1(C)C=CC=CC=1>[Cl:20][C:21]1[C:22]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35]([O:36][C@@H:37]([CH2:42][O:43][CH2:44][CH3:45])[C:38]([NH:19][C:16]4[CH:15]=[CH:14][C:13]([S:12][CH3:11])=[CH:18][N:17]=4)=[O:39])=[C:30]3[CH:29]=[N:28]2)=[N:23][CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 151797975-(Methylsulfanyl)pyridin-2-amineHCID 16682925TrimethylaluminumHCID 57504615methyl (2S)-2-[1-(3-chloropyridin-2-yl)pyrazolo[4,5-e]pyrimidin-4-yl]oxy-3-ethoxypropanoate

Product 1

HCID 57504501HCID 57504501, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

2M Trimethylaluminium in hexane (0.457 mL, 0.91 mmol) was added to 5-(methylthio)pyridin-2-amine (CAS no. 77618-99-6) (0.111 g, 0.79 mmol) in toluene (22 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxypropanoate (Intermediate L2) (0.300 g, 0.79 mmol) in toluene (6 mL) was added dropwise at this temperature. After the addition was complete, the solution was allowed to warm to ambient temperature and was then heated at reflux for 16 hours. The mixture was allowed to cool to ambient temperature and left standing for 2 days. The reaction mixture was concentrated, diluted with ethyl acetate (100 mL) then washed with saturated brine (50 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 3% MeOH in DCM to afford the product.

Workup

  1. customat 0° C.
  2. additionAfter the addition
  3. temperatureto warm to ambient temperature
  4. temperaturewas then heated
  5. temperatureat reflux for 16 hours
  6. temperatureto cool to ambient temperature
  7. waitleft
  8. waitstanding for 2 days
  9. concentrationThe reaction mixture was concentrated
  10. additiondiluted with ethyl acetate (100 mL)
  11. washthen washed with saturated brine (50 mL)
  12. dry with materialThe organic layer was dried (MgSO4)
  13. customevaporated
  14. customThe residue was purified by flash silica chromatography
  15. washeluting with 0 to 3% MeOH in DCM
  16. customto afford the product

Sources & evidence

ORD record
ord-893e4c1469ec46178be0b13a7c6cd6f8
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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