1-Hydroxybenzotriazole → benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamate

HRID 1184039Notes

Reaction equation

HRID 1184039 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:16]12[CH2:25][CH:20]3[CH2:21][CH:22]([CH2:24][C:18]([OH:26])([CH2:19]3)[CH2:17]1)[CH2:23]2)[C:13](O)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C@H:27]12[CH2:32][C@H:31]1[CH2:30][C@@H:29]([C:33]([NH2:35])=[O:34])[NH:28]2.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[C:33]([C@@H:29]1[CH2:30][C@H:31]2[C@H:27]([CH2:32]2)[N:28]1[C:13](=[O:14])[C@@H:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:16]12[CH2:25][CH:20]3[CH2:21][CH:22]([CH2:24][C:18]([OH:26])([CH2:19]3)[CH2:17]1)[CH2:23]2)(=[O:34])[NH2:35]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 11506821(1S,3S,5S)-2-Azabicyclo(3.1.0)hexane-3-carboxamideHCID 86703400(2S)-2-{[(benzyloxy)carbonyl]amino}-2-(3-hydroxyadamantan-1-yl)acetic acid

Product 1

HCID 86703401benzyl N-[(1S)-2-[(1S,3S,5S)-3-carbamoyl-2-azabicyclo[3.1.0]hexan-2-yl]-1-(3-hydroxyadamantan-1-yl)-2-oxo ethyl]carbamateYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

(2S)-2-{[(Benzyloxy)carbonyl]amino}-2-(3-hydroxyadamantan-1-yl)acetic acid of Formula-XIV (20 gm), 1-ethyl-3-(3-dimethyl aminoporpyl)carbodiimide (13.8 gm), (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide of formula-III (14.8 gm) and 1-hydroxy benzotriazole (10.2 gm) were dissolved in N,N-dimethyl formamide (80 ml). The reaction mixture was cooled to about 20° C. Addition of N,N-diisopropylethylamine (15.8 gm) was then carried out for 15 min. The reaction mixture was stirred for 4 hrs and the solvent was distilled off. To the residue 2N HCl solution was added. Aqueous phase was extracted with ethyl acetate. Organic phase was washed with NaHCO3 solution, dried and evaporated to yield 23.3 gms (90%) of title product. MP: 105-106° C., H1NMR (300 MHz, CDCl3): 0.81 (dd, 1H), 0.96 (m, 1H), 1.46-1.82 (m, 12H), 1.93 (s, 1H), 2.2 (m, 3H), 2.45 (dd, 1H), 3.6 (m, 1H), 4.5-4.61 (dd, 1H), 4.76-4.86 (dd, 1H), 5.0 (s, 2H), 5.34 (d, 1H), 5.69 (s, 1H), 5.82-5.85 (dd, 1H), 6.83-6.89 (s, 1H), 7.31-7.35 (m, 5H).

Workup

  1. distillationthe solvent was distilled off
  2. additionTo the residue 2N HCl solution was added
  3. extractionAqueous phase was extracted with ethyl acetate
  4. washOrganic phase was washed with NaHCO3 solution
  5. customdried
  6. customevaporated

Sources & evidence

ORD record
ord-d1e4f3e7fe7e436f91fab7d91393b1e3
Source dataset
uspto-grants-2014_03
Patent number
US08664443B2

Reaction notes

Loading…