Diisopropylethylamine → {2-[3-(2-Ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionylamino]-ethyl}-carbamic acid tert-butyl ester

HRID 2047321Notes

Reaction equation

HRID 2047321 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([N:21]([CH:23]([CH3:25])[CH3:24])[CH3:22])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:26])[C:4]=1[CH2:27][CH2:28][C:29](O)=[O:30])[CH3:2].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:74]([NH:81][CH2:82][CH2:83][NH2:84])([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75]>CN(C=O)C>[C:77]([O:76][C:74](=[O:75])[NH:81][CH2:82][CH2:83][NH:84][C:29](=[O:30])[CH2:28][CH2:27][C:4]1[C:5]([CH3:26])=[CH:6][C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([N:21]([CH:23]([CH3:25])[CH3:24])[CH3:22])[CH:15]=3)[O:11][N:10]=2)=[CH:8][C:3]=1[CH2:1][CH3:2])([CH3:78])([CH3:79])[CH3:80]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 187201N-BOC-ethylenediamineHCID 2724699PyBOPHCID 685780763-(2-Ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionic acid

Product 1

HCID 68578269{2-[3-(2-Ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionylamino]-ethyl}-carbamic acid tert-butyl esterYield 80.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(2-ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionic acid (41 mg, 0.097 mmol) and DIPEA (38 mg, 0.291 mmol) in DMF (3 mL) is added PyBOP (56 mg, 0.107 mmol) at 0° C. The mixture is stirred for 15 min at 0° C. before N-BOC-ethylenediamine (17 mg, 0.107 mmol) is added and stirring is continued for 1 h at 0° C. The reaction is quenched with 2 mL water, and the mixture is diluted in sat. aq. NaHCO3-solution, and extracted three times with diethyl ether. The combined org. extracts are dried over MgSO4, filtered and dried to give crude {2-[3-(2-ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionylamino]-ethyl}-carbamic acid tert-butyl ester (44 mg). This material is dissolved in 4 N HCl in dioxane (5 mL) and the mixture is stirred at rt for 18 h. The solvent is evaporated and the crude product is purified on prep. TLC plates with DCM containing 6% of 7 N NH3 in methanol to give N-(2-amino-ethyl)-3-(2-ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionamide (23 mg) as a yellow solid; LC-MS: tR=0.72 min; [M+1]+=465.32.

Workup

  1. additionis added
  2. customThe reaction is quenched with 2 mL water
  3. additionthe mixture is diluted in sat. aq. NaHCO3-solution
  4. extractionextracted three times with diethyl ether
  5. dry with materialextracts are dried over MgSO4
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-75000f026d9c48d2988a108f06b8d03b
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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