Diisopropylethylamine → HCID 87402917, compound

HRID 588920Notes

Reaction equation

HRID 588920 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:20])([CH3:19])[C:10]([NH:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH3:28][O:29][C:30](=[O:44])[C:31]([CH3:43])([CH3:42])[NH:32][C:33](=[O:41])[C@H:34]([CH2:36][O:37][C:38]#[C:39][CH3:40])[NH2:35].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>[CH3:28][O:29][C:30](=[O:44])[C:31]([CH3:43])([CH3:42])[NH:32][C:33](=[O:41])[C@H:34]([CH2:36][O:37][C:38]#[C:39][CH3:40])[NH:35][C:14](=[O:16])[C:13]([CH3:18])([CH3:17])[NH:12][C:10](=[O:11])[C:9]([CH3:20])([CH3:19])[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 27960291-Hydroxybenzotriazole hydrateHCID 53812573HCID 53812573, compoundHCID 87404217HCID 87404217, compound

Product 1

HCID 87402917HCID 87402917, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
0 °C

Procedure

N-tert-butoxycarbonyl α,α-dimethylglycyl α,α-dimethylglycine 4 (3.37 g, 11.7 mmol) and O-propynyl L-seryl α,α-dimethylglycine methyl ester trifluoroacetate 15 (4.16 g, 11.7 mmol) were dissolved in DMF (30 mL). A solution of N,N-diisopropylethylamine (1.51 g, 11.7 mmol) in DMF (20 mL) was added and the solution cooled to 0° C. (ice bath). HOBt hydrate (1.79 g, 11.7 mmol) and then EDC hydrochloride (2.46 g, 12.8 mmol) were added in portions together with more DMF (10 mL). The reaction mixture was stirred for 5 min at 0° C. after which the ice bath was removed and stirring continued for 44 h at room temperature. The solvent was evaporated and the residue taken up in EtOAc (300 mL). The solution was washed with 1 M HCl (3×120 mL), 7.5% (w/w) K2CO3 solution (3×120 mL) and saturated brine (120 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a slightly yellowish solid (5.18 g). The solid was purified by flash column chromatography (eluent: CH2Cl2/acetone (4:1)) affording the title compound as a white solid (4.58 g, 77%); 1H NMR (300 MHz, DMSO-d6) δ 8.11 (s, 1H, NH(Aib)), 7.73 (s, 1H, NH(Aib)), 7.66 (d, J=8.1 Hz, 1H, NH(propSer)), 7.31 (s, 1H, NH(Aib1)), 4.33 (td, J=8.6, 3.8 Hz, 1H, CαH), 4.03 (t, J=2.8 Hz, 1H, CH2CCH), 3.81 (dd, J=9.9, 3.6 Hz, 1H, CHH), 3.59 (dd, J=9.3, 9.3 Hz, 1H, CHH), 3.54 (s, 3H, OCH3), 3.41 (t, J=2.3 Hz, 1H, CCH), 1.41 (s, 9H, (CH3)3), 1.37 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.33 (s, 3H, CH3), 1.29 (s, 3H, CH3), 1.28 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 175.2, 174.2, 174.0, 168.7, 155.5, 79.8, 79.0, 77.2, 68.5, 57.3, 55.9, 55.8, 55.0, 52.9, 51.7, 28.1, 26.7, 25.4, 24.6, 24.6, 24.1, 23.2; HRMS (m/z): [M+Na]+ calcd. for C24H40N4O8Na, 535.2743. found, 535.2728; Anal. Calcd. for C24H40N4O8: C, 56.23; H, 7.87; N, 10.93. Found: C, 56.0; H, 7.8; N, 10.8.

Workup

  1. customwas removed
  2. customThe solvent was evaporated
  3. washThe solution was washed with 1 M HCl (3×120 mL), 7.5% (w/w) K2CO3 solution (3×120 mL) and saturated brine (120 mL)
  4. dry with materialThe solution was dried with anhydrous MgSO4
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-e8976d0d1aa54c85aeafeed5be367bb1
Source dataset
uspto-grants-2016_01
Patent number
US09227995B2

Reaction notes

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