Hydrochloric Acid → N-[3-methyl-N-(2,2-diphenylacetyl)-L-phenylalanyl]-S-trityl-L-cysteinamide

HRID 276727Notes

Reaction equation

HRID 276727 reaction equation
COC(C1C=C(COC[C@@H:14]([NH:17][C:18](=[O:44])[C@H:19]([CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[C:39]([CH3:43])[CH:38]=2)[NH:20][C:21](=[O:35])[CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15]#[N:16])C=CC=1)=O.O.[OH:46]N1C2C=CC=CC=2N=N1.CN1CCOCC1.CN(C)CCCN=C=NCC.Cl.[C:75]([S:94][CH2:95][C@@H](C(N)=O)N)([C:88]1[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=1)([C:82]1[CH:87]=[CH:86][CH:85]=[CH:84][CH:83]=1)[C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1>C(Cl)Cl>[CH3:43][C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[CH2:36][C@@H:19]([C:18]([NH:17][C:14](=[O:46])[C@H:15]([CH2:95][S:94][C:75]([C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)([C:88]1[CH:89]=[CH:90][CH:91]=[CH:92][CH:93]=1)[C:82]1[CH:83]=[CH:84][CH:85]=[CH:86][CH:87]=1)[NH2:16])=[O:44])[NH:20][C:21](=[O:35])[CH:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 44432703(2R)-2-amino-3-((triphenylmethyl)sulfanyl)propanamideHCID 86608564N-[2-[(3-(methoxycarbonyl)phenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nalpha-(2,2-diphenylacetyl)-L-phenylalaninamide

Product 1

HCID 69266013N-[3-methyl-N-(2,2-diphenylacetyl)-L-phenylalanyl]-S-trityl-L-cysteinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-methyl-N-(2,2-diphenylacetyl-L-phenylalanine (see example 302, 1.0 g, 2.68 mmol), 1-hydroxybenzotriazole hydrate (0.41 g, 2.68 mmol) and N-methylmorpholine (0.74 mL, 6.69 mmol) in CH2Cl2 (80 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (0.77 g, 4.02 mmol) in one portion. After stirring 30 minutes at room temperature, S-trityl-L-cysteinamide (0.97 g, 2.68 mmol) is added to the solution in one portion, and the solution is stirred for 16 hours. The solution is evaporated, and the residue partitioned between water (80 mL) and ethyl acetate (80 mL). The aqueous layer is washed with EtOAc (2×80 mL), and the combined organic layers are then washed with 1 N HCl (100 mL), saturated aqueous NaHCO3 (1×50 mL), water (1×50 mL) and brine (1×50 mL), dried over MgSO4, and evaporated. The residue is triturated with Et2O/hexane (1:1) to yield N-[3-methyl-N-(2,2-diphenylacetyl)-L-phenylalanyl]-S-trityl-L-cysteinamide as a white solid.

Workup

  1. stirringthe solution is stirred for 16 hours
  2. customThe solution is evaporated
  3. customthe residue partitioned between water (80 mL) and ethyl acetate (80 mL)
  4. washThe aqueous layer is washed with EtOAc (2×80 mL)
  5. washthe combined organic layers are then washed with 1 N HCl (100 mL), saturated aqueous NaHCO3 (1×50 mL), water (1×50 mL) and brine (1×50 mL)
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue is triturated with Et2O/hexane (1:1)

Sources & evidence

ORD record
ord-507de8f9dbad465ca60d6a9eda7c5cbc
Source dataset
uspto-grants-2002_03
Patent number
US06353017B1

Reaction notes

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