Diisopropylethylamine → (S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester

HRID 1469625Notes

Reaction equation

HRID 1469625 reaction equation
Cl.C(OC(=O)[C@@H](C)CC(N)CC1C=CC(C2C=CC=C(Cl)C=2)=CC=1)C.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[NH2:38][CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41].CCN(C(C)C)C(C)C.[CH2:56]([O:58][C:59](=[O:81])[C@@H:60]([CH3:80])[CH2:61][CH:62]([N:77]=[C:78]=[O:79])[CH2:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([Cl:76])[CH:71]=2)=[CH:66][CH:65]=1)[CH3:57]>CN(C=O)C>[CH2:56]([O:58][C:59](=[O:81])[C@@H:60]([CH3:80])[CH2:61][CH:62]([N:77]=[C:78]=[O:79])[CH2:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([Cl:76])[CH:71]=2)=[CH:66][CH:65]=1)[CH3:57].[CH2:56]([O:58][C:59](=[O:81])[C@@H:60]([CH3:80])[CH2:61][CH:62]([NH:77][C:78]([NH:38][CH2:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])=[O:79])[CH2:63][C:64]1[CH:69]=[CH:68][C:67]([C:70]2[CH:75]=[CH:74][CH:73]=[C:72]([Cl:76])[CH:71]=2)=[CH:66][CH:65]=1)[CH3:57]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 151417Glycine tert-butyl esterHCID 67505771HCID 67505771, compound2×HCID 86648210(S)-5-(3'-Chloro-biphenyl-4-yl)-4-isocyanato-2-methyl-pentanoic acid ethyl ester

Product 2

HCID 67506149(S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3'-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl esterHCID 86648210(S)-5-(3'-Chloro-biphenyl-4-yl)-4-isocyanato-2-methyl-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-5-(3′-Chloro-biphenyl-4-yl)-4-isocyanato-2-methyl-pentanoic acid ethyl ester is prepared from (S)-4-amino-5-(3′-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester hydrochloride (Intermediate 31) and triphosgene analogous to the procedure described for Example 6-1. Next, to a solution of tert-butyl 2-aminoacetate (140 mg, 1.065 mmol) in DMF (5 mL) is added DIEA (344 mg, 2.66 mmol). The solution is stirred at room temperature for 5 minutes then (S)-5-(3′-chloro-biphenyl-4-yl)-4-isocyanato-2-methyl-pentanoic acid ethyl ester (330 mg, 0.887 mmol) is added. The mixture is stirred at room temperature for 2 hours then the solvent is removed under reduced pressure to give (S)-4-(3-tert-butoxycarbonylmethyl-ureido)-5-(3′-chloro-biphenyl-4-yl)-2-methyl-pentanoic acid ethyl ester which is used directly in the following reaction.

Workup

  1. stirringThe mixture is stirred at room temperature for 2 hours
  2. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-3ecc4bbd851047d7a7d88cf23aa9294b
Source dataset
uspto-grants-2015_04
Patent number
US09006249B2

Reaction notes

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