Diisopropylethylamine → HCID 68578138, compound

HRID 2047320Notes

Reaction equation

HRID 2047320 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]([OH:31])=O)[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]([O:78][C:79](=[O:83])[CH2:80][CH2:81][NH2:82])([CH3:77])([CH3:76])[CH3:75]>CN(C=O)C>[C:74]([O:78][C:79](=[O:83])[CH2:80][CH2:81][NH:82][C:29](=[O:31])[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]([CH3:24])[CH3:25])[CH3:22])[CH:15]=3)[O:11][N:10]=2)=[CH:8][C:3]=1[CH2:1][CH3:2])([CH3:77])([CH3:76])[CH3:75]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 4192171tert-Butyl 3-aminopropanoateHCID 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 68578138HCID 68578138, compoundYield 82.9%

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 (43 mg, 0.101 mmol) and DIPEA (40 mg, 0.304 mmol) in DMF (3 mL) is added PyBOP (58 mg, 0.111 mmol) at 0° C. The mixture is stirred for 15 min at 0° C. before β-alanine tert.-butyl ester (20 mg, 0.111 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 3-[3-(2-ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionylamino]-propionic acid tert-butyl ester (46 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 18% of 7 N NH3 in methanol to give 3-[3-(2-ethyl-4-{5-[2-(isopropyl-methyl-amino)-6-methyl-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-propionylamino]-propionic acid (37 mg) as a yellow solid; LC-MS: tR=0.86 min; [M+1]+=494.24.

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-3aec9ddfcb764737a2eb5c74ad9091b1
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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