Tert-butoxycarbonylalanine → 2,2-Dimethylpropionic acid 2-{(S)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl ester

HRID 243035Notes

Reaction equation

HRID 243035 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([CH2:16][CH2:17][O:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:11]1.[C:25]([O:29][C:30]([NH:32][C@@H:33]([CH3:37])[C:34](O)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:25]([O:29][C:30]([NH:32][C@@H:33]([CH3:37])[C:34]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][C@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([CH2:16][CH2:17][O:18][C:19](=[O:24])[C:20]([CH3:21])([CH3:23])[CH3:22])[CH2:11]1)=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681574342,2-Dimethylpropionic acid 2-[(S)-3-(2-amino-5-fluorophenylamino)piperidin-1-yl]ethyl ester

Product 1

HCID 681571232,2-Dimethylpropionic acid 2-{(S)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluorophenylamino]piperidin-1-yl}ethyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled mixture of 2,2-dimethylpropionic acid 2-[(S)-3-(2-amino-5-fluorophenylamino)piperidin-1-yl]ethyl ester (1.464 g, 4.34 mmol), (S)-2-tert-butoxycarbonylaminopropionic acid (0.904 g, 4.77 mmol) and HOAt (0.591 g, 4.34 mmol) in DCM (40 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.0 g, 5.21 mmol) portion wise over 10 min. The reaction mixture was stirred in the ice bath for 2 h, then diluted with DCM, washed with 2M Na2CO3 then water. The organic fractions were dried (Na2SO4) then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 40-70% EtOAc in cyclohexane) affording the title compound as a dark red gum (2.054 g, 93%). LCMS (Method B): RT 2.46 min [M+H]+ 509.

Workup

  1. washwashed with 2M Na2CO3
  2. dry with materialThe organic fractions were dried (Na2SO4)
  3. concentrationthen concentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 40-70% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-a71d5b8f85fc4216832d98fcbd975f14
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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