Piperidine → HCID 86714503, compound

HRID 409118Notes

Reaction equation

HRID 409118 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:26][C@@H:27]3[CH2:31][CH2:30][CH2:29][N:28]3[C:32](=[O:36])[CH2:33][C:34]#[N:35])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=4)=[CH:13][C:12]=3[F:25])[C:3]=12.[CH3:37][C:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:41])[CH:39]=O.N1CCCCC1>O1CCOCC1.CC(O)=O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:26][C@@H:27]3[CH2:31][CH2:30][CH2:29][N:28]3[C:32](=[O:36])[C:33]([C:34]#[N:35])=[CH:41][C:38]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:37])[CH3:39])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=4)=[CH:13][C:12]=3[F:25])[C:3]=12

Participants

6

Reactant 3

HCID 8082PiperidineHCID 14578674tert-butyl N-(2-methyl-1-oxopropan-2-yl)carbamateHCID 86714504HCID 86714504, compound

Product 1

HCID 86714503HCID 86714503, compoundYield 18.2%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-((S)-2-((4-amino-3-(2-fluoro-4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidin-1-yl)-3-oxopropanenitrile (245 mg, 0.5 mmol, 1 equiv) and tert-butyl 2-methyl-1-oxopropan-2-ylcarbamate (935 mg, 5 mmol, 10 equiv) in dioxane (30 mL) was added 0.5 mL piperidine, 1 drop AcOH and 2 g of 4A molecular sieves. The resulting mixture was stirred for 6 h at 110° C. The solids was filtered out, the filtrate was diluted with 200 mL of ethyl acetate, washed with brine, dried over Na2SO4, concentrated and purified with silica gel column (ethyl acetate/MeOH 10/1) to give 60 mg of tert-butyl 5-((S)-2-((4-amino-3-(2-fluoro-4-(3-fluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidin-1-yl)-4-cyano-2-methyl-5-oxopent-3-en-2-ylcarbamate as white solid.

Workup

  1. filtrationThe solids was filtered out
  2. additionthe filtrate was diluted with 200 mL of ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. custompurified with silica gel column (ethyl acetate/MeOH 10/1)

Sources & evidence

ORD record
ord-954426bffb2e464892fce500f0a7c4d7
Source dataset
uspto-grants-2014_06
Patent number
US08759358B1

Reaction notes

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