1-Pyrrolidineethanamine → HCID 178512240, compound

HRID 1270986Notes

Reaction equation

HRID 1270986 reaction equation
C(O[C:6](=O)[NH:7][C@@H:8]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:9][C:10](=[O:19])[NH:11][CH2:12][CH2:13][N:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1)(C)(C)C.C(OC(N[C@@H]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)CC(O)=O)=O)(C)(C)C.N1(CCN)CCCC1.[CH:54]1[CH:55]=[CH:56][C:57]2[N:62](O)N=N[C:58]=2[CH:59]=1.CN1CCOCC1.CC[N:73]=[C:74]=[N:75]CCCN(C)C.Cl>CN(C=O)C.O>[C:54]1([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:59]=[CH:58][C:57]([N:62]=[C:6]([NH:75][C:74]#[N:73])[NH:7][C@@H:8]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:9][C:10]([NH:11][CH2:12][CH2:13][N:14]2[CH2:15][CH2:16][CH2:17][CH2:18]2)=[O:19])=[CH:56][CH:55]=1

Participants

9

Reactant 6

HCID 13441-PyrrolidineethanamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7009108(3R)-3-[(tert-Butoxycarbonyl)amino]-3-phenylpropanoic acidHCID 69430297HCID 69430297, compound

Product 1

HCID 178512240HCID 178512240, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

[(R)-1-Phenyl-2-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester. To a solution of (R)-3-tert-butoxycarbonylamino-3-phenyl-propionic acid (0.54 g, 2.04 mmol), 2-pyrrolidin-1-yl-ethylamine (0.35 g, 3.06 mmol), HOBt (0.41 g, 3.06 mmol) and 4-methylmorpholine (0.41 g, 4.08 mmol) in DMF (10 mL), was added EDCl (0.59 g, 3.06 mmol), and the resulting solution was stirred under N2 at rt for 20 h. The solution was diluted with H2O (75 mL) and was extracted with EtOAc (3×75 mL). The combined extracts were washed with brine (100 mL), dried (Na2SO4) and filtered, and the solvent was removed. The crude product was purified by column chromatography on silica gel using a gradient of 2–30% (MeOH (1% NH4OH)/CH2Cl2) to afford 0.65 g. (88%) of the desired product as a white solid. Rf=0.34 (10% MeOH (1% NH4OH)/CH2Cl2). MS (electrospray): mass calculated for C20H31N3O3, 361.24; m/z found, 362.2 [M+H]+, 745.4 [2M+Na]+. 1H NMR (400 MHz, CDCl3): 7.32–7.28 (m, 4H), 7.24–7.20 (m, 1H), 6.37 (br s, 1H), 6.14 (br s, 1H), 5.01 (br s, 1H), 3.21 (dd, J=11.2, 5.7 Hz, 2H), 2.74–2.67 (m, 1H), 2.59 (dd, J=14, 5.9 Hz, 1H), 2.49–2.38 (m, 6H), 1.76–1.67 (m, 4H), 1.41 (s, 9H).

Workup

  1. extractionwas extracted with EtOAc (3×75 mL)
  2. washThe combined extracts were washed with brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was removed
  6. customThe crude product was purified by column chromatography on silica gel using a gradient of 2–30% (MeOH (1% NH4OH)/CH2Cl2)
  7. customto afford 0.65 g

Sources & evidence

ORD record
ord-2a19ea2444c442e6bb60b545c712c636
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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