Diisopropylethylamine → HCID 87403496, compound

HRID 588914Notes

Reaction equation

HRID 588914 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:14])([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH3:22][O:23][C:24](=[O:35])[C:25]([CH3:34])([CH3:33])[NH:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[NH2:29].C(N(CC)C(C)C)(C)C.C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[CH3:22][O:23][C:24](=[O:35])[C:25]([CH3:34])([CH3:33])[NH:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[NH:29][C:10](=[O:12])[C:9]([CH3:14])([CH3:13])[NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 27960291-Hydroxybenzotriazole hydrateHCID 87403533HCID 87403533, compound

Product 1

HCID 87403496HCID 87403496, compoundYield 52.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl α,α-dimethylglycine 1 (3.20 g, 15.7 mmol) and α,α-dimethylglycyl α,α-dimethylglycine methyl ester trifluoroacetate 5 (4.98 g, 15.7 mmol) were dissolved in DMF (40 mL). N,N-Diisopropylethylamine (2.06 g, 15.9 mmol) and HOBt hydrate (2.41 g, 15.7 mmol) were added together with more DMF (10 mL). The solution was cooled to 0° C. (ice bath) and EDC hydrochloride (3.32 g, 17.3 mmol) added in portions together with additional DMF (10 mL). The reaction mixture was stirred for 15 min at 0° C., after which the ice bath was removed and stirring continued for 43 h at room temperature. The solvent was evaporated and the residue taken up in EtOAc (150 mL). The solution was washed with 1 M aqueous H2SO4 (3×50 mL), 7.5% (w/w) K2CO3 solution (3×50 mL) and saturated brine (50 mL). After dilution with EtOAc (100 mL) the solution was dried with anhydrous MgSO4 and the solvent evaporated affording an off-white solid (3.20 g, 52%), with spectral characteristics in accordance with literature data6; 1H NMR (200 MHz, DMSO-d6) δ 7.59 (s, 2H, NH(Aib2)/NH(Aib3)), 7.21 (s, 1H, NH(Aib1)), 3.53 (s, 3H, OCH3), 1.41 (s, 9H, (CH3)3), 1.33 (s, 6H, CH3), 1.28 (s, 6H, CH3), 1.25 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 174.4, 173.8, 173.2, 155.1, 78.7, 55.8, 55.4, 54.9, 51.6, 28.1, 24.8, 24.6, 24.6; HRMS (m/z): [M+Na]+ calcd. for C18H33N3O6Na, 410.2267. found, 410.2269; Anal. Calcd. for C18H33N3O6: C, 55.80; H, 8.58; N, 10.84. Found: C, 55.9; H, 8.7; N, 11.0.

Workup

  1. customafter which the ice bath was removed
  2. stirringstirring
  3. waitcontinued for 43 h at room temperature
  4. customThe solvent was evaporated
  5. washThe solution was washed with 1 M aqueous H2SO4 (3×50 mL), 7.5% (w/w) K2CO3 solution (3×50 mL) and saturated brine (50 mL)
  6. dry with materialAfter dilution with EtOAc (100 mL) the solution was dried with anhydrous MgSO4
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-43054c8d23604a5cb83ab0d551a953c0
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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