2-Amino-5-chloropyridine → HCID 57504559, compound

HRID 1098252Notes

Reaction equation

HRID 1098252 reaction equation
C[Al](C)C.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][CH2:21][CH2:22][CH2:23][C@H:24]([O:29][C:30]1[N:35]=[CH:34][N:33]=[C:32]2[N:36]([C:39]3[C:44]([Cl:45])=[CH:43][CH:42]=[CH:41][N:40]=3)[N:37]=[CH:38][C:31]=12)[C:25](OC)=[O:26])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1>[Si:13]([O:20][CH2:21][CH2:22][CH2:23][C@H:24]([O:29][C:30]1[N:35]=[CH:34][N:33]=[C:32]2[N:36]([C:39]3[C:44]([Cl:45])=[CH:43][CH:42]=[CH:41][N:40]=3)[N:37]=[CH:38][C:31]=12)[C:25]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([Cl:5])=[CH:11][N:10]=1)=[O:26])([C:16]([CH3:18])([CH3:19])[CH3:17])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 661742-Amino-5-chloropyridineHCID 16682925TrimethylaluminumHCID 57504618HCID 57504618, compound

Product 1

HCID 57504559HCID 57504559, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of trimethylaluminium (2M in toluene) (0.795 mL, 1.59 mmol) was added dropwise to a stirred solution of 5-chloropyridin-2-amine (178 mg, 1.38 mmol) in toluene (5 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 15 minutes. A solution of (2S)-methyl 5-(tert-butyldimethylsilyloxy)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanoate (Intermediate O2) (680 mg, 1.38 mmol) in toluene (5 mL) was added dropwise. The resulting solution was stirred at 0° C. for 10 minutes allowed to warm to ambient temperature and then heated at reflux for 18 hours. The reaction mixture was allowed to cool to r.t. and concentrated. The residue was diluted with ethyl acetate and treated with 1M citric acid (2ml). The layers were separated and the organics were washed with water and brine, dried (MgSO4) and concentrated to a yellow foam, (2S)-5-(tert-butyldimethylsilyloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanamide (693 mg, 85%). m/z (ES+) (M+H)+=588.46; HPLC tR=3.54 min.

Workup

  1. stirringThe resulting solution was stirred at 0° C. for 10 minutes
  2. temperatureto warm to ambient temperature
  3. temperatureheated
  4. temperatureat reflux for 18 hours
  5. temperatureto cool to r.t.
  6. concentrationconcentrated
  7. additionThe residue was diluted with ethyl acetate
  8. additiontreated with 1M citric acid (2ml)
  9. customThe layers were separated
  10. washthe organics were washed with water and brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated to a yellow foam, (2S)-5-(tert-butyldimethylsilyloxy)-N-(5-chloropyridin-2-yl)-2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pentanamide (693 mg, 85%)

Sources & evidence

ORD record
ord-ae23d792b48744d0a1d9026e0e34c50f
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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