Triethylamine → 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine

HRID 393441Notes

Reaction equation

HRID 393441 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C@@H:7]([C:26]([OH:28])=[O:27])[NH:8]C(OCC2C3C=CC=CC=3C3C2=CC=CC=3)=O)=[CH:4][CH:3]=1.[C:31](C1NC=CN=1)(C1NC=CN=1)=[O:32].C(N(CC)CC)C.Cl.[C:51]([C:53]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)#[N:52]>ClCCl.CN(C1C=CN=CC=1)C.CN1CCCC1=O>[C:51]([C:53]1([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[CH2:54][CH2:55][N:56]([C:31]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:6][C@@H:7]([C:26]([OH:28])=[O:27])[NH2:8])=[CH:29][CH:30]=2)=[O:32])[CH2:57][CH2:58]1)#[N:52]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 30849734-Phenylpiperidine-4-carbonitrile hydrochlorideHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 7019927Fmoc-4-Amino-L-phenylalanine2×

Product 1

HCID 539777144-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-Amino-N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-phenylalanine on Wang resin (300 mg, 0.228 mmol) obtained from Example 62 was placed in a vessel fitted with a glass frit and was washed with dichloromethane (2×10 mL), methanol (2×10 mL) and dichloromethane (2×10 mL). To the resin was added carbonyl diimidazole (0.22 g, 1.4 mmol) and triethylamine (0.38 mL, 2.7 mmol) in 3 mL of dichloromethane. The mixture was agitated over night. The mixture was then filtered and washed with dichloromethane (3×5 mL). To the resin was added 4-cyano-4-phenylpiperidine hydrochloride (0.25 g, 1.14 mmol) and DMAP (0.14 g, 1.14 mmol) in 3 mL of N-methylpyrrolidinone. The resulting mixture was agitated for 3 hours. The reaction mixture was then filtered and washed with dichloromethane (2×10 mL), methanol (2×10 mL), dimethylformamide (2×10 mL) and methanol (2×10 mL). Cleavage of the Fmoc group was effected with 25% piperidine in N-methylpyrrolidinone (2×15 min to give 4-[[(4-cyano-4-phenyl-1-piperidinyl)carbonyl]amino]-L-phenylalanine on Wang resin.

Workup

  1. customfitted with a glass frit
  2. washwas washed with dichloromethane (2×10 mL), methanol (2×10 mL) and dichloromethane (2×10 mL)
  3. filtrationThe mixture was then filtered
  4. washwashed with dichloromethane (3×5 mL)
  5. stirringThe resulting mixture was agitated for 3 hours
  6. filtrationThe reaction mixture was then filtered
  7. washwashed with dichloromethane (2×10 mL), methanol (2×10 mL), dimethylformamide (2×10 mL) and methanol (2×10 mL)
  8. custom2×15 min

Sources & evidence

ORD record
ord-66bf96368e654c51a75b32740da816bb
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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