Dimethylformamide → HCID 89928131, compound

HRID 879979Notes

Reaction equation

HRID 879979 reaction equation
[C:1]([O:5][C:6](=[O:36])[C@@H:7]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[NH:8][C:9](=[O:28])[C:10](=[C:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[NH:11]NC#C)([CH3:4])([CH3:3])[CH3:2].[NH:37]([CH2:40][CH3:41])[CH2:38][CH3:39].I[C:43]1[CH:48]=CC=C[CH:44]=1.[CH3:49]N(C=O)C>CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:1]([O:5][C:6](=[O:36])[C@@H:7]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[NH:8][C:9](=[O:28])[C:10](=[C:15]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[N:11]([C:38]1[CH:39]=[CH:49][CH:41]=[CH:40][N:37]=1)[CH2:48][C:43]#[CH:44])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8021DiethylamineHCID 11575IodobenzeneHCID 89928302HCID 89928302, compound

Product 1

HCID 89928131HCID 89928131, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A solution of benzhydrylidene aza-propargylglycinyl-D-phenylalaninyl tert-butyl ester (1, 500 mg, 1.04 mmol) in 10 mL of a 1:1 (v/v) DMF:Et2NH mixture was treated with Pd(PPh3)2Cl2 (73 mg, 0.104 mmol), CuI (40 mg, 0.208 mmol), and iodobenzene (0.15 mL, 1.35 mmol) under inert atmosphere. The solution was stirred for 12 h, diluted with 40 mL of EtOAc, and washed with saturated NaHCO3 (3×50 mL). After drying over Na2SO4, the solution was filtered, and concentrated under reduced pressure to a residue, which was purified by silica gel chromatography using 30% Et2O in petroleum ether to give aza-dipeptide 18a as orange foam (504 mg, 87%): Rf 0.41 (6:4 petroleum ether:Et2O); [α]D20 −24.1 (c 1.06, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.47 (9H, s), 3.30-3.21 (2H, m), 4.20 (1H, d, J=18.0 Hz), 4.54 (1H, d, J=17.9), 4.88-4.82 (1H, m), 7.59-7.20 (20H, m). 13C NMR (100 MHz, CDCl3) δ 171.3, 158.2, 157.7, 139.3, 137.0, 136.2, 132.0, 130.4, 130.2, 130.1, 129.8, 129.1, 129.0, 128.8, 128.7, 128.6, 127.3, 123.4, 84.8, 84.5, 82.3, 55.5, 38.9, 36.4, 28.5. HRMS m/z 558.2769, (M+H)+ calcd for [C36H36N3O3]+: 558.2751. IR (neat) 1731, 1679, 1488, 1366, 1150, 756, 691.

Workup

  1. washwashed with saturated NaHCO3 (3×50 mL)
  2. dry with materialAfter drying over Na2SO4
  3. filtrationthe solution was filtered
  4. concentrationconcentrated under reduced pressure to a residue, which
  5. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-74ef33277016404b95d49b8f5a7a15df
Source dataset
uspto-grants-2015_03
Patent number
US08993515B2

Reaction notes

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