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

HRID 243025Notes

Reaction equation

HRID 243025 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.CCN=C=NCCCN(C)C.Cl>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 681571932,2-Dimethylpropionic acid 2-[(R)-3-(2-amino-5-fluorophenylamino)piperidin-1-yl]ethyl ester

Product 1

HCID 681578402,2-Dimethylpropionic acid 2-{(R)-3-[2-((S)-2-tert-butoxycarbonylaminopropionylamino)-5-fluoro-phenylamino]piperidin-1-yl}ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled mixture of 2,2-dimethylpropionic acid 2-[(R)-3-(2-amino-5-fluorophenylamino)piperidin-1-yl]ethyl ester (500 mg, 1.48 mmol), (S)-2-tert-butoxycarbonylaminopropionic acid (309 mg, 1.63 mmol) and HOAt (202 mg, 1.48 mmol) in DCM (30 mL) was added N-(3-dimethylaminopropyl)-n′-ethylcarbodiimide hydrochloride (341 mg, 1.78 mmol). The reaction mixture was stirred in the ice bath for 1.5 h, then diluted with DCM, washed with 2M Na2CO3 and then water. The organic fraction was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 50-100% EtOAc in cyclohexane) affording the title compound as a purple gum (quantitative). LCMS (Method B): RT 2.50 min [M+H]+ 509.

Workup

  1. washwashed with 2M Na2CO3
  2. dry with materialThe organic fraction was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 50-100% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-b743dfda1ada4625a3e0b507d54c31ae
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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