Diisopropylethylamine → HCID 86658400, compound

HRID 1874631Notes

Reaction equation

HRID 1874631 reaction equation
[NH2:1][CH2:2][C@H:3]([NH:17][C:18](=[O:27])[C@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:20])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:6][CH:5]=1.[C:28]([NH:35][C@H:36]([C:41](O)=[O:42])[C@H:37]([CH2:39][CH3:40])[CH3:38])([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([O-])(O)=O.[Na+]>ClCCl>[CH3:38][C@@H:37]([CH2:39][CH3:40])[C@H:36]([NH:35][C:28](=[O:29])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[C:41]([NH:1][CH2:2][C@@H:3]([C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH:12]([CH3:16])[CH2:13][CH2:14][CH3:15])=[CH:8][CH:9]=1)[NH:17][C:18](=[O:27])[C@H:19]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH3:20])=[O:42]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2724762tert-Butoxycarbonyl-L-isoleucineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58466401HCID 58466401, compound

Product 1

HCID 86658400HCID 86658400, compoundYield 60.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of (2S)-N-((1R)-2-amino-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (200 mg, 0.543 mmol), prepared according to the procedure described in example 5, in dichloromethane (4 mL) was cooled to 0° C. To this solution, Boc-L-isoleucine (188 mg, 0.814 mmol), N,N-diisopropylethylamine (0.569 mL, 3.26 mmol) and HATU (310 mg, 0.814 mmol) were added. The ice-water bath was removed and reaction mixture was stirred at room temperature for 3 h. The mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (60 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30→40% ethyl acetate in hexanes) to afford t-butyl (2S,3S)-3-methyl-1-((2R)-2-(4-(2-methylpentyloxy)phenyl)-2-((S)-2-phenylpropanamido)ethylamino)-1-oxopentan-2-ylcarbamate (190 mg, 60% yield) as a colorless solid: LRMS (ESI) m/e 582.4 [(M+H)+, calcd for C34H52N3O5 582.4].

Workup

  1. customThe ice-water bath was removed
  2. customreaction mixture
  3. customThe mixture was transferred to a separatory funnel
  4. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (30→40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bea1ccd687fe4c119e00b1b8c190620c
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

Loading…