Hydrochloric Acid → tert-Butyl 4-{3-({[2-({1-[(1-Adamantylamino)carbonyl]-(1S)-3-benzyloxy-3-oxopropyl}amino)-2-oxoethyl]amino}carbonyl)-5-[1-(tert-butoxycarbonyl)-4-piperidyl]pentyl}tetrahydro-1(2H)-pyridinecarboxylate

HRID 2271220Notes

Reaction equation

HRID 2271220 reaction equation
ClC(OCC(C)C)=O.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][CH:24]([CH2:32][CH2:33][CH:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]2)[C:25]([NH:27][CH2:28][C:29](O)=[O:30])=[O:26])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].CN1CCOCC1.FC(F)(F)C(O)=O.[NH2:61][C@H:62]([C:74]([NH:76][C:77]12[CH2:86][CH:81]3[CH2:82][CH:83]([CH2:85][CH:79]([CH2:80]3)[CH2:78]1)[CH2:84]2)=[O:75])[CH2:63][C:64]([O:66][CH2:67][C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)=[O:65].Cl>C(OCC)(=O)C>[C:77]12([NH:76][C:74]([C@@H:62]([NH:61][C:29](=[O:30])[CH2:28][NH:27][C:25]([CH:24]([CH2:23][CH2:22][CH:19]3[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])[CH2:17][CH2:18]3)[CH2:32][CH2:33][CH:34]3[CH2:35][CH2:36][N:37]([C:40]([O:42][C:43]([CH3:44])([CH3:46])[CH3:45])=[O:41])[CH2:38][CH2:39]3)=[O:26])[CH2:63][C:64]([O:66][CH2:67][C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)=[O:65])=[O:75])[CH2:78][CH:79]3[CH2:85][CH:83]([CH2:82][CH:81]([CH2:80]3)[CH2:86]1)[CH2:84]2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 15433187HCID 15433187, compound2×HCID 131723055benzyl (3S)-3-amino-4-(1-adamantylamino)-4-oxobutanoate trifluoroacetate

Product 1

HCID 131723054tert-Butyl 4-{3-({[2-({1-[(1-Adamantylamino)carbonyl]-(1S)-3-benzyloxy-3-oxopropyl}amino)-2-oxoethyl]amino}carbonyl)-5-[1-(tert-butoxycarbonyl)-4-piperidyl]pentyl}tetrahydro-1(2H)-pyridinecarboxylateYield 68.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Isobutyl chloroformate (1.7 g, 12.4 mmol) is added, at room temperature, to a solution of 2-[(4-[1-(tert-butoxycarbonyl)-4-piperidyl]-2-{2-[1-(tert-butoxycarbonyl)-4-piperidyl]ethyl}butanoyl)amino]acetic acid (compound 4) (6.9 g, 11 mmol) in 150 ml of ethyl acetate and N-methylmorpholine (5 g, 49.5 mmol). A white suspension is obtained. After stirring for 10 minutes, a solution of benzyl (3S)-3-amino-4-(1-adamantylamino)-4-oxobutanoate trifluoroacetate (6.9 g, 11.2 mmol) in 20 ml of ethyl acetate is added. Stirring is continued at room temperature for 18 hours. 2N hydrochloric acid is added. The organic phase is washed with water, dried over sodium sulphate and evaporated to give the crude product, which is purified by flash chromatography (20/1 dichloromethane/methanol) to give 6.6 g of a beige-coloured solid.

Workup

  1. customA white suspension is obtained
  2. stirringStirring
  3. waitis continued at room temperature for 18 hours
  4. washThe organic phase is washed with water
  5. dry with materialdried over sodium sulphate
  6. customevaporated
  7. customto give the crude product, which
  8. customis purified by flash chromatography (20/1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-cf2943e436ac4abc93e076275a7bf034
Source dataset
uspto-grants-2001_12
Patent number
US06333338B1

Reaction notes

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