1-Pyrrolidineethanamine → HCID 58843188, compound

HRID 1270989Notes

Reaction equation

HRID 1270989 reaction equation
C(O[C:6](=[O:23])[NH:7][C@H:8]([CH2:12][C:13](=[O:22])[NH:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)[CH:9]([CH3:11])[CH3:10])(C)(C)C.[CH:24]1[CH:25]=[CH:26][C:27]2N(O)N=[N:30][C:28]=2[CH:29]=1.CCN=C=N[CH2:39][CH2:40][CH2:41]N(C)C.Cl.[C:46](OC(N[C@@H](C(C)C)CC(O)=O)=O)(C)([CH3:48])[CH3:47].N1(CCN)CCCC1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O.O>[N:17]1([CH2:16][CH2:15][NH:14][C:13](=[O:22])[CH2:12][C@@H:8]([NH:7][C:6]([NH:30][C:28]2[CH:29]=[CH:24][C:25]([C:39]3[CH:40]=[CH:41][CH:48]=[CH:46][CH:47]=3)=[CH:26][CH:27]=2)=[O:23])[CH:9]([CH3:10])[CH3:11])[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

10

Reactant 6

HCID 13441-PyrrolidineethanamineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2761559Boc-L-beta-homovalineHCID 69432149HCID 69432149, compound

Product 1

HCID 58843188HCID 58843188, compoundYield 78%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

{(R)-2-Methyl-1-[(2-pyrrolidin-1-yl-ethylcarbamoyl)-methyl]-propyl}-carbamic acid tert-butyl ester. HOBT (0.351 g, 2.6 mmol) and EDCl (0.5 g, 2.6 mmol) were added to a solution of (R)-3-tert-butoxycarbonylamino-4-methyl-pentanoic acid (0.4 g, 1.7 mmol) in DMF (8.5 mL). Following the addition of a solution of 2-pyrrolidin-1-yl-ethylamine (0.3 g, 2.6 mmol) in DMF (2 mL), N-methyl-morpholine (0.26 g, 2.6 mmol) was added dropwise. The reaction mixture was stirred at rt overnight. Water (20 mL) and EtOAc (30 mL) were then added to the mixture. The aqueous layer was extracted with EtOAc (3×40 mL). The combined organic layers were washed with 1 N NaOH (2×20 mL) and brine (40 mL), dried (MgSO4), and concentrated. Purification by column chromatography [0–20% (1% NH4OH/MeOH)/CH2Cl2] afforded 0.44 g (78%) of the desired product. MS (electrospray): mass calculated for C17H33N3O3, 327.25; m/z found, 328.3 [M+H]+. 1H NMR (400 MHz, CDCl3): 6.22 (s, 1H), 5.30 (d, J=6.7 Hz, 1H), 3.66–3.59 (m, 1H), 3.44–3.36 (m, 1H), 3.35–3.27 (m, 1H), 2.59–2.56 (m, 2H), 2.52 (m, 4H), 2.42–2.40 (m, 2H), 1.87–1.74 (m, 8H), 1.43 (s, 9H), 0.93 (t, J=6.3, 6H).

Workup

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

Sources & evidence

ORD record
ord-9fe270316542468e978cdd5c681d24af
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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