Diisopropylcarbodiimide → Fmoc-Cys(Acm)-Phg-OtBu

HRID 352286Notes

Reaction equation

HRID 352286 reaction equation
[NH:1]([C:13]([O:15][CH2:16][CH:17]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:14])[C@H:2]([C:10](O)=[O:11])[CH2:3][S:4][CH2:5][NH:6][C:7]([CH3:9])=[O:8].C1C=CC2N(O)N=NC=2C=1.[NH2:40][C@H:41]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.CC(C)N=C=NC(C)C>C(Cl)Cl>[NH:1]([C:13]([O:15][CH2:16][CH:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:24]2[C:29]1=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:14])[C@H:2]([C:10]([NH:40][C@H:41]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:11])[CH2:3][S:4][CH2:5][NH:6][C:7]([CH3:9])=[O:8]

Participants

6

Reactant 4

HCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 128799S-((Acetylamino)methyl)-N-((9H-fluoren-9-ylmethoxy)carbonyl)-L-cysteineHCID 7016394(S)-tert-Butyl 2-amino-2-phenylacetate

Product 1

HCID 131724456Fmoc-Cys(Acm)-Phg-OtBu

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of Fmoc-Cys(Acm)-OH (855 mg, 2 mmol) in 4 ml dry DCM at 0° C., HOBt (270 mg, 2 mmol) was added. Then an ice-cold solution of H-Phg-OtBu (415 mg, 2 mmol) in 4 ml of dry DCM was added. Subsequently, DIC (319 μl, 2 mmol) was introduced dropwise. After 1 h at 0° C. and 4 h at 4° C., the solution was evaporated under vacuum. The residue was dissolved in 50 ml EtOAc and washed with sat. aq. NaHCO3, 0.5 M HCl and water. After drying and evaporation of the organic phase, the residue was chromatographed on silica gel to give the protected dipeptide 1 as a foam. Yield 1.14 g (95%), Rf 0.35 (DCM/MeOH, 95:5). 1H NMR (CDCL3): δ1.45 (9H, s, tBu), 1.92 (3H, s, CH3 Acm), 2.71-3.1 (2H, m, CβH2 Cys), 3.8 (1H, m, CoH Cys) 4.2-4.5 (5H,m, CH2 Acm. CH—CH2 Fmoc), 4.56-4.85 (3H, m, CoH Phg, Fmoc), 5.4 (1H, d, J=7.3 Hz, NH) 6.47 (1H, d, J=8.4 Hz, NH), 7.2-8.05 (14H, Fmoc+Phg aromatic, NH Acm). 13C NMR (CDCl3): δ23.7 (CH2, Acm), 27.7 (3×CH3, tBu), 34.9 (Cβ, Cys), 41.1 (CH2, Acm), 41.9 (CH2, Fmoc), 57.4 (CαPhg), 83.7 (Cq tBu), 119.7-127.5 (aromatic, Fmoc, Phg), 141.0 and 143.6 (4C, Fmoc), 156.6 (CO, Fmoc), 170.2 (CO, Cys), 173.5 (2×CO, Acm, tBu ester).

Workup

  1. custom4 h at 4° C., the solution was evaporated under vacuum
  2. dissolutionThe residue was dissolved in 50 ml EtOAc
  3. washwashed with sat. aq. NaHCO3, 0.5 M HCl and water
  4. customAfter drying
  5. customevaporation of the organic phase
  6. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-f32c917b548d4c488f3d876cda770854
Source dataset
uspto-grants-2004_06
Patent number
US06747009B2

Reaction notes

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