Triphenylphosphine → HCID 23560784, compound

HRID 1058457Notes

Reaction equation

HRID 1058457 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][C:21]1[CH:29]=[C:28]([N:30]2[C:34]([NH:35][CH2:36][C:37]3[CH:45]=[CH:44][CH:43]=[C:42]4[C:38]=3[CH:39]=[CH:40][NH:41]4)=[N:33][N:32]=[N:31]2)[CH:27]=[C:26]([CH3:46])[C:22]=1[C:23]([OH:25])=O.ClN1C(=O)CCC1=O.[CH3:55][O:56][C:57](=[O:66])[CH:58]([P:60]([O:64][CH3:65])([O:62][CH3:63])=[O:61])[NH2:59].COC(=O)C(P(OC)(OC)=O)NC(OCC1C=CC=CC=1)=O>ClCCl>[CH3:55][O:56][C:57](=[O:66])[CH:58]([P:60]([O:62][CH3:63])([O:64][CH3:65])=[O:61])[NH:59][C:23](=[O:25])[C:22]1[C:26]([CH3:46])=[CH:27][C:28]([N:30]2[C:34]([NH:35][CH2:36][C:37]3[CH:45]=[CH:44][CH:43]=[C:42]4[C:38]=3[CH:39]=[CH:40][NH:41]4)=[N:33][N:32]=[N:31]2)=[CH:29][C:21]=1[CH3:20]

Participants

7

Reactant 5

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetateHCID 11084793Methyl 2-amino-2-(dimethoxyphosphoryl)acetateHCID 18673035HCID 18673035, compound

Product 1

HCID 23560784HCID 23560784, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Triphenylphosphine (1.31 g, 5 mmol) is added to a suspension of give 2,6-dimethyl-4-[5-[(1H-indol-4-yl)methylamino]tetrazol-1-yl]benzoic acid (Example 329; 1.81 g, 5 mmol) in dichloromethane (25 mL) at 25° C. The mixture is cooled to 0° C. and N-chlorosuccinimide (0.668 g, 5 mmol) is added. After stirring 15 min at 0° C., the mixture is stirred for an additional 15 min at 25° C. and then a solution of rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (3.01 g, 10 mmol) in dichloromethane (5 mL) is added in one portion. The reaction is stirred for 5 h, then the precipitated amine hydrochloride is filtered off, washed with dichloromethane and discarded. The filtrate is washed with 1N hydrochloric acid solution (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL), then is dried (MgSO4) and concentrated under reduced pressure. The residue is chromatographed over silica gel (increasing percentages of ethyl acetate in petroleum ether) and the appropriate fractions are combined and evaporated to yield rac.-N-[2,6-dimethyl-4-[5-[(1H-indol-4-yl)methylamino]tetrazol-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester.

Workup

  1. stirringthe mixture is stirred for an additional 15 min at 25° C.
  2. additionis added in one portion
  3. stirringThe reaction is stirred for 5 h
  4. filtrationthe precipitated amine hydrochloride is filtered off
  5. washwashed with dichloromethane
  6. washThe filtrate is washed with 1N hydrochloric acid solution (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and brine (50 mL)
  7. dry with materialis dried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is chromatographed over silica gel (increasing percentages of ethyl acetate in petroleum ether)
  10. customevaporated

Sources & evidence

ORD record
ord-bd15697a66264f679af8dd2abdff04c3
Source dataset
uspto-grants-2003_02
Patent number
US06515124B2

Reaction notes

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