Diisopropylethylamine → (S,E)-2-(3-(2-(tert-butoxycarbonylamino)-7-methoxy-7-oxohept-5-enamido)-2-oxopyridin-1(2H)-yl)acetic acid

HRID 58323

Reaction equation

HRID 58323 reaction equation
C([O:5][C:6](=[O:35])[CH2:7][N:8]1[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][C:15](=[O:33])[C@@H:16]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:17][CH2:18]/[CH:19]=[CH:20]/[C:21]([O:23][CH3:24])=[O:22])[C:9]1=[O:34])(C)(C)C.CCN(C(C)C)C(C)C.C(ON1C(=O)CCC1=O)(OC(C)(C)C)=O>ClCCl.FC(F)(F)C(O)=O.CN(C=O)C>[C:29]([O:28][C:26]([NH:25][C@@H:16]([CH2:17][CH2:18]/[CH:19]=[CH:20]/[C:21]([O:23][CH3:24])=[O:22])[C:15]([NH:14][C:10]1[C:9](=[O:34])[N:8]([CH2:7][C:6]([OH:35])=[O:5])[CH:13]=[CH:12][CH:11]=1)=[O:33])=[O:27])([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 83168Carbonic acid, 1,1-dimethylethyl 2,5-dioxo-1-pyrrolidinyl esterHCID 118104203(S,E)-Methyl 7-(1-(2-tert-butoxy-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl-amino)-6-(tert-butoxycarbonylamino)-7-oxohept-2-enoate

Product 1

HCID 89925798(S,E)-2-(3-(2-(tert-butoxycarbonylamino)-7-methoxy-7-oxohept-5-enamido)-2-oxopyridin-1(2H)-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

590 mg of (S,E)-methyl 7-(1-(2-tert-butoxy-2-oxoethyl)-2-oxo-1,2-dihydropyridin-3-yl-amino)-6-(tert-butoxycarbonylamino)-7-oxohept-2-enoate (ZED1209, 1.20 mmol) are dissolved in 10 mL of dichloromethane and to this solution 10 mL of trifluoroacetic acid is added. It is stirred at RT for 1 h. The solvent is removed in vacuo and the residue is dried under high vacuum. The obtained oil is further reacted without purification. The oil is taken up in 15 mL of DMF and treated with 173 μL of DIPEA. By successive addition of DIPEA the pH value is adjusted to ca. 7. To this solution, 285 mg of Boc-OSu (1.1 eq) are added and stirred at RT overnight. The solvent is removed in vacuo and the residue is purified by preparative HPLC (30% ACN in water, 8 mL/min, gradient 1% pro min).

Workup

  1. additionis added
  2. customThe solvent is removed in vacuo
  3. customthe residue is dried under high vacuum
  4. customThe obtained oil is further reacted without purification
  5. stirringstirred at RT overnight
  6. customThe solvent is removed in vacuo
  7. customthe residue is purified by preparative HPLC (30% ACN in water, 8 mL/min, gradient 1% pro min)

Sources & evidence

ORD record
ord-743b7f1dad3644efb3a46de49b7848db
Source dataset
uspto-grants-2016_09
Patent number
US09434763B2

Linked notes

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