1,1'-Carbonyldiimidazole → tert-Butyl (S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-2-[3-((8S,11R)-8-isopropyl-10-oxo-6-oxa-1,9,14-triazabicyclo[11.2.1]hexadeca-13(16),14-dien-11-yl)ureido]propionate

HRID 1023007Notes

Reaction equation

HRID 1023007 reaction equation
[NH2:1][C@@H:2]1[CH2:16][C:15]2=[CH:17][N:12]([CH:13]=[N:14]2)[CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C@H:5]([CH:18]([CH3:20])[CH3:19])[NH:4][C:3]1=[O:21].[C:22](N1C=CN=C1)(N1C=CN=C1)=[O:23].[NH2:34][C@@H:35]([CH2:43][C:44]1[CH:45]=[N:46][C:47]([NH:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[CH:48][CH:49]=1)[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C=O)C>[C:54]([O:53][C:51]([NH:50][C:47]1[N:46]=[CH:45][C:44]([CH2:43][C@H:35]([NH:34][C:22]([NH:1][C@@H:2]2[CH2:16][C:15]3=[CH:17][N:12]([CH:13]=[N:14]3)[CH2:11][CH2:10][CH2:9][CH2:8][O:7][CH2:6][C@H:5]([CH:18]([CH3:19])[CH3:20])[NH:4][C:3]2=[O:21])=[O:23])[C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])=[CH:49][CH:48]=1)=[O:52])([CH3:57])([CH3:56])[CH3:55]

Participants

5

Reactant 3

HCID 682631,1'-Carbonyldiimidazole2×HCID 58360487tert-Butyl (S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)propionateHCID 67028858(8S,11R)-11-Amino-8-isopropyl-6-oxa-1,9,14-triazabicyclo[11.2.1]hexadeca-13(16),14-dien-10-one

Product 1

HCID 86655970tert-Butyl (S)-3-(6-tert-butoxycarbonylaminopyridin-3-yl)-2-[3-((8S,11R)-8-isopropyl-10-oxo-6-oxa-1,9,14-triazabicyclo[11.2.1]hexadeca-13(16),14-dien-11-yl)ureido]propionateYield 21,603,088%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 56 mg (190 pmol) of (8S,11R)-11-amino-8-isopropyl-6-oxa-1,9,14-triazabicyclo[11.2.1]hexadeca-13(16),14-dien-10-one from step D in 5 ml of DMF was cooled to 0° C. and, while stirring, 32 mg (194 μmol) of 1,1′-carbonyldiimidazole were added. The mixture was stirred for 30 min, and then 64 mg (190 pmol) of tert-butyl(S)-2-amino-3-(6-tert-butoxycarbonylaminopyridin-3-yl)propionate were added, and the mixture was warmed to RT. After standing overnight, the same amount of 1,1′-carbonyldiimidazole was again added, and the mixture was stirred for a further 24 h. It was then concentrated and purified by preparative HPLC. 27 mg of the desired compound were obtained.

Workup

  1. stirringThe mixture was stirred for 30 min
  2. stirringthe mixture was stirred for a further 24 h
  3. concentrationIt was then concentrated
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-febcc7702b0b4b38a2b62c56417e5015
Source dataset
uspto-grants-2014_05
Patent number
US08722655B2

Reaction notes

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