4-Methylmorpholine → HCID 131726470, compound

HRID 1354872Notes

Reaction equation

HRID 1354872 reaction equation
[NH:1]([C:36]([O:38][CH2:39][CH:40]=[CH2:41])=[O:37])[C@@H:2]([C:4]([NH:6][C@H:7]([C:18]([NH:20][C@H:21]([C:33]([OH:35])=[O:34])[CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][CH2:30][CH:31]=[CH2:32])=[O:28])=[O:19])[CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)=[O:5])[CH3:3].CN1CC[O:46]CC1.C(OC(Cl)=O)C(C)C.[NH2:57][C:58]1[CH:65]=[CH:64][C:61]([CH2:62][OH:63])=[CH:60][CH:59]=1>O1CCCC1>[NH:1]([C:36]([O:38][CH2:39][CH:40]=[CH2:41])=[O:37])[C@@H:2]([C:4]([NH:6][C@H:7]([C:18]([NH:20][C@H:21]([C:33]([OH:35])=[O:34])[CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:27]([O:29][CH2:30][CH:31]=[CH2:32])=[O:28])=[O:19])[CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)=[O:5])[CH3:3].[CH:60]1[C:61]([C:62]([OH:46])=[O:63])=[CH:64][CH:65]=[C:58]([NH2:57])[CH:59]=1

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 693314-Aminobenzyl alcoholHCID 10864740HCID 10864740, compound

Product 1

HCID 131726470HCID 131726470, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of 239 mg (0.419 mmol) Aloc-D-Ala-Trp-Lys(Aloc)-OH 28 was dissolved in dry tetrahydrofuran under an argon atmosphere and cooled to −40° C. N-methylmorpholine (48.3 μl, 1.05 equiv) and isobutylchloroformate (57.0 μl, 1.05 equiv) were added. The reaction mixture was stirred for 2 hours at a temperature below −30° C. A solution of 4-aminobenzyl alcohol (51.5 mg, 1.00 equiv) and N-methylmorpholine (50.6 μl, 1.1 equiv) in dry THF was added dropwise to the reaction mixture. After 2 hours tetrahydrofuran was evaporated and dichloromethane was added. The organic layer was washed with saturated sodium bicarbonate, a 0.5 N potassium bisulphate solution and brine, dried (Na2SO4) and evaporated to afford 265 mg (94%) of the desired product 29 as a cream coloured powder. 1H-NMR (300 MHz, CDCl3/CD3OD): δ 1.00–1.62 (m, 9H, CH3-Ala and 3 CH2-Lys), 2.90–3.70 (m, 4H, N—CH2-Lys and CH2-Trp), 4.48–4.92 (m, 7H, 2 Hα and 4 Aloc), 4.72 (s, 2H, CH2—OH), 5.00–5.50 (m, 5H, 4 Aloc and Hα), 5.35–6.05 (m, 2H, Aloc), 6.80–7.83 (m, 9H, aromatic) ppm; MS (FAB) m/e 677 (M+H)+, 699 (M+Na)+.

Workup

  1. customAfter 2 hours tetrahydrofuran was evaporated
  2. additiondichloromethane was added
  3. washThe organic layer was washed with saturated sodium bicarbonate
  4. dry with materiala 0.5 N potassium bisulphate solution and brine, dried (Na2SO4)
  5. customevaporated

Sources & evidence

ORD record
ord-c0d55e3695814700b00ff0d96485c246
Source dataset
uspto-grants-2007_05
Patent number
US07223837B2

Reaction notes

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