1-(Propan-2-yl)piperidin-4-amine → HCID 10392328, compound

HRID 900247Notes

Reaction equation

HRID 900247 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([NH2:10])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].C[Al](C)C.CC[O:17][C:18]([C:20]1[N:21]([CH2:32][C:33]2[CH:37]=[C:36]([C:38]3[S:39][C:40]([Cl:43])=[CH:41][CH:42]=3)[O:35][N:34]=2)[CH:22]=[C:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[N:24]=1)=O>C(Cl)Cl>[C:28]([O:27][C:25]([C:23]1[N:24]=[C:20]([C:18](=[O:17])[NH:10][CH:7]2[CH2:8][CH2:9][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:5][CH2:6]2)[N:21]([CH2:32][C:33]2[CH:37]=[C:36]([C:38]3[S:39][C:40]([Cl:43])=[CH:41][CH:42]=3)[O:35][N:34]=2)[CH:22]=1)=[O:26])([CH3:31])([CH3:29])[CH3:30]

Participants

5

Reactant 3

HCID 31633331-(Propan-2-yl)piperidin-4-amineHCID 16682925TrimethylaluminumHCID 69111631HCID 69111631, compound

Product 1

HCID 10392328HCID 10392328, compoundYield 28.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1-isopropyl-piperidin-4-ylamine (142 mg) in DCM (4 mL) was added trimethyl aluminium (0.5 mL, 2M solution in hexanes) dropwise under an Ar atmosphere. The mixture was stirred for 15 min at RT. A solution of 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-imidazole-2,4-dicarboxylic acid 4-tert-butyl ester 2-ethyl ester [example 1, (i)] (438 mg) in DCM (4 mL) was added dropwise and stirring was continued for 17 h at RT and 3 h at 35° C. After cooling the reaction was quenched by dropwise addition of 1M aqueous KHSO4 solution, concentrated, taken up in 6N HCL and extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC. The fractions containing the product were evaporated to provide 154 mg of 1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-imidazole-4-carboxylic acid tert-butyl ester (example 2) as its trifluoroacetate salt. MS (ESI+): m/e=534, chloro pattern.

Workup

  1. stirringstirring
  2. waitwas continued for 17 h at RT and 3 h at 35° C
  3. temperatureAfter cooling the reaction
  4. customwas quenched by dropwise addition of 1M aqueous KHSO4 solution
  5. concentrationconcentrated
  6. extractionextracted with ethyl acetate
  7. washThe combined organic extracts were washed with water and brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative HPLC
  11. additionThe fractions containing the product
  12. customwere evaporated

Sources & evidence

ORD record
ord-9c19da9635bd4d7c9eaa473908538f28
Source dataset
uspto-grants-2008_04
Patent number
US07358268B2

Reaction notes

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