Triethylamine → Benzyl (R)-3-(2-benzyloxycarbonylaminoethylsulfanyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionate

HRID 1022999Notes

Reaction equation

HRID 1022999 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C@@H:14]([CH2:25][S:26][CH2:27][CH2:28][NH:29][C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31])[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].C(N(CC)CC)C.[NH2:47][C@@H:48]1[CH2:63][C:62]2=[CH:64][CH:65]=[C:59]([CH:60]=[CH:61]2)[O:58][CH2:57][CH2:56][CH2:55][CH2:54][O:53][CH2:52][C@H:51]([CH:66]([CH3:68])[CH3:67])[NH:50][C:49]1=[O:69]>CN(C=O)C>[CH2:33]([O:32][C:30]([NH:29][CH2:28][CH2:27][S:26][CH2:25][C@H:14]([NH:13][C:1]([NH:47][C@@H:48]1[CH2:63][C:62]2=[CH:61][CH:60]=[C:59]([CH:65]=[CH:64]2)[O:58][CH2:57][CH2:56][CH2:55][CH2:54][O:53][CH2:52][C@H:51]([CH:66]([CH3:67])[CH3:68])[NH:50][C:49]1=[O:69])=[O:2])[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])=[O:31])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 58360483(9S,12R)-12-Amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-oneHCID 58360484Benzyl (R)-2-amino-3-(2-benzyloxycarbonylaminoethylsulfanyl)propionate

Product 1

HCID 67320524Benzyl (R)-3-(2-benzyloxycarbonylaminoethylsulfanyl)-2-[3-((9S,12R)-9-isopropyl-11-oxo-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-12-yl)ureido]propionateYield 29.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 166 mg (1.02 mmol) of 1,1′-carbonyldiimidazole in 8 ml of DMF was mixed with 515 mg (1.02 mmol) of the trifluoroacetate from step B and 0.57 ml (415 mg, 4.10 mmol) of triethylamine. A solution of 328 mg (1.02 mmol) of (9S,12R)-12-amino-9-isopropyl-2,7-dioxa-10-azabicyclo[12.2.2]octadeca-1(17),14(18),15-trien-11-one (1-1E) in 8 ml of DMF was added to this mixture under argon, and the mixture was stirred at RT overnight. The reaction mixture was then concentrated and separated by preparative HPLC. The required fractions were combined and freed of acetonitrile. The resulting aqueous solution was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate, filtered and concentrated. 222 mg of the title compound were obtained.

Workup

  1. concentrationThe reaction mixture was then concentrated
  2. customseparated by preparative HPLC
  3. extractionThe resulting aqueous solution was extracted with ethyl acetate
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8acb09ca0ff943b0a8a1d35e1c7a6c94
Source dataset
uspto-grants-2014_05
Patent number
US08722655B2

Reaction notes

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