1-Pyrrolidineethanamine → HCID 11272398, compound

HRID 1270996Notes

Reaction equation

HRID 1270996 reaction equation
C(OC(=O)N[C@@H:8]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23]C=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.[CH:28]1[CH:29]=[CH:30][C:31]2[N:36](O)N=N[C:32]=2[CH:33]=1.CCN=C=NC[CH2:44][CH2:45][N:46](C)C.[ClH:49].C([O:54]C(N[C@@H](CC1C=CC=CC=1)CC(O)=O)=O)(C)(C)C.N1(CCN)[CH2:74][CH2:73][CH2:72][CH2:71]1.CN1[CH2:84][CH2:83][O:82]CC1>CN(C=O)C.CCOC(C)=O.O>[Cl:49][C:73]1[CH:74]=[CH:84][C:83]([O:82][C:28]2[CH:33]=[CH:32][C:31]([NH:36][CH2:44][C:45]([NH:46][C@@H:9]([CH2:8][C:20]3[CH:21]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:10]([NH:11][CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][CH2:17][CH2:18]3)=[O:19])=[O:54])=[CH:30][CH:29]=2)=[CH:71][CH:72]=1

Participants

10

Reactant 6

HCID 13441-PyrrolidineethanamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2761538(S)-3-(Boc-amino)-4-phenylbutyric acidHCID 69429341HCID 69429341, compound

Product 1

HCID 11272398HCID 11272398, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

[(S)-1-Benzyl-2-(2-pyrrolidin-1-yl-ethylcarbamoyl)-ethyl]-carbamic acid tert-butyl ester. HOBT (0.318 g, 2.36 mmol) and EDCl (0.452 g, 2.36 mmol) were added to a solution of (S)-3-tert-butoxycarbonylamino-4-phenyl-butyric acid (0.27 g, 2.36 mmol) in DMF (16 mL). Following the addition of a solution of 2-pyrrolidin-1-yl-ethylamine (0.44 g, 1.6 mmol) in DMF (2 mL), N-methyl-morpholine (0.32 g, 3.16 mmol) was added dropwise. The reaction mixture was stirred at rt overnight. Water (30 mL) and EtOAc (50 mL) were then added to the mixture. The aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with 1 N NaOH (2×40 mL) and brine (50 mL), dried (MgSO4), and concentrated. Purification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] afforded 0.5 g (84%) of the desired product. MS (electrospray): mass calculated for C21H33N3O3, 375.25; m/z found, 376.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.32–7.21 (m, 5H), 6.22 (s, 1H), 5.78 (s, 1H), 4.14–4.06 (m, 1H), 3.40 (d, J=5.3 Hz, 2H), 3.02–3.00 (m, 1H), 2.83–2.77 (m, 1H), 2.63 (s, 2H), 2.57 (s, 3H), 2.41 (dd, J=14.5, 4.3 Hz, 1H), 2.27 (dd, J=14.5, 5.03 Hz, 1H), 1.82 (s, 4H), 1.43 (s, 9H).

Workup

  1. additionwas added dropwise
  2. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  3. washThe combined organic layers were washed with 1 N NaOH (2×40 mL) and brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customPurification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2]

Sources & evidence

ORD record
ord-c3b34da978ef443793e157b613061b19
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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