Triethylamine → tert-butyl(S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-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 1023002Notes

Reaction equation

HRID 1023002 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[NH2:13][C@@H:14]([CH2:22][C:23]1[CH:24]=[N:25][C:26]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:27][CH:28]=1)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C(N(CC)CC)C.[NH2:44][C@@H:45]1[CH2:60][C:59]2=[CH:61][CH:62]=[C:56]([CH:57]=[CH:58]2)[O:55][CH2:54][CH2:53][CH2:52][CH2:51][O:50][CH2:49][C@H:48]([CH:63]([CH3:65])[CH3:64])[NH:47][C:46]1=[O:66]>CN(C=O)C>[C:33]([O:32][C:30]([NH:29][C:26]1[N:25]=[CH:24][C:23]([CH2:22][C@H:14]([NH:13][C:1]([NH:44][C@@H:45]2[CH2:60][C:59]3=[CH:58][CH:57]=[C:56]([CH:62]=[CH:61]3)[O:55][CH2:54][CH2:53][CH2:52][CH2:51][O:50][CH2:49][C@H:48]([CH:63]([CH3:64])[CH3:65])[NH:47][C:46]2=[O:66])=[O:2])[C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])=[CH:28][CH:27]=1)=[O:31])([CH3:36])([CH3:35])[CH3:34]

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 58360487tert-Butyl (S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)propionate

Product 1

HCID 67320386tert-butyl(S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

112 mg (0.69 mmol) of 1,1′-carbonyldiimidazole were added to a mixture of 234 mg (0.69 mmol) of tert-butyl(S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-propionate and 106 μl (77 mg, 0.76 mmol) of triethylamine in 2.5 ml of DMF. The solution was stirred at RT for 1 h, before a solution of 222 mg (0.69 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 2.5 ml of DMF was added. The mixture was left to stand overnight and then concentrated and partitioned between water and ethyl acetate. The organic phase was separated off, dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC. The required fractions were combined, freed of acetonitrile, made slightly alkaline with sodium bicarbonate and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated.

Workup

  1. additionwas added
  2. waitThe mixture was left
  3. concentrationconcentrated
  4. custompartitioned between water and ethyl acetate
  5. customThe organic phase was separated off
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC
  10. extractionextracted with ethyl acetate
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-69a49e24f5cf419eb390bc961f81d365
Source dataset
uspto-grants-2014_05
Patent number
US08722655B2

Reaction notes

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