Sodium Hydroxide → HCID 178442041, compound

HRID 540394Notes

Reaction equation

HRID 540394 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[CH2:24]([C:31]([OH:33])=O)[CH2:25][C:26]1[N:30]=[CH:29][NH:28][CH:27]=1.[NH2:34][C@H:35]([CH2:54][C:55]1[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][CH:56]=1)[C:36]([N:38]1[CH2:41][C:40]([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])([C:42]2[CH:47]=[CH:46][C:45]([F:48])=[CH:44][CH:43]=2)[CH2:39]1)=[O:37].[OH-].[Na+]>CN(C)C=O.C(N(CC)CC)C>[F:48][C:45]1[CH:46]=[CH:47][C:42]([C:40]2([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH2:39][N:38]([C:36](=[O:37])[C@H:35]([NH:34][C:31](=[O:33])[CH2:24][CH2:25][C:26]3[N:30]=[CH:29][NH:28][CH:27]=3)[CH2:54][C:55]3[CH:60]=[CH:59][C:58]([O:61][CH3:62])=[CH:57][CH:56]=3)[CH2:41]2)=[CH:43][CH:44]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66988297(R)-2-Amino-3-(4-methoxyphenyl)-1-(3-pentyl-3-(4-fluorophenyl)azetidin-1-yl)-propan-1-oneHCID 178479756HCID 178479756, compound

Product 1

HCID 178442041HCID 178442041, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8471TriethylamineSolvent

Procedure

600 mg (1.86 mmol) of TBTU and 0.45 ml of triethylamine are added to a solution containing 330 mg (1.86 mmol) of desamino-histidine hydrochloride in 5 ml of dimethylformamide. After stirring for 15 minutes, 590 mg (1.55 mmol) of (R)-2-amino-3-(4-methoxyphenyl)-1-(3-pentyl-3-(4-fluorophenyl)azetidin-1-yl)-propan-1-one dissolved in 5 ml of dimethylformamide are added. The reaction medium is stirred at ambient temperature for 3 days. The reaction is stopped by adding a 1N solution of sodium hydroxide and then extracted with a 1/1 heptane/ethyl acetate mixture. The organic phases are combined and dried over sodium sulphate. After filtration, the solvents are evaporated off and the residue is then purified by silica gel chromatography (eluent 85/15 dichloromethane/methanol). 490 mg of N-[(R)-2-[3-(4-fluorophenyl)-3-pentylazetidin-1-yl]-1-(4-methoxybenzyl)-2-oxoethyl]-3-(1H-imidazol-4-yl)-propionamide are obtained in the form of a white powder with a yield of 61%.

Workup

  1. additionare added
  2. stirringThe reaction medium is stirred at ambient temperature for 3 days
  3. extractionextracted with a 1/1 heptane/ethyl acetate mixture
  4. dry with materialdried over sodium sulphate
  5. filtrationAfter filtration
  6. customthe solvents are evaporated off
  7. customthe residue is then purified by silica gel chromatography (eluent 85/15 dichloromethane/methanol)

Sources & evidence

ORD record
ord-a7471c4989fc46b7873e58c88fab5d35
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

Loading…