1,2-Dichloroethane → (S)-2-(3-Biphenyl-4-yl-ureido)-N-(3-pyrrolidin-1-yl-propyl)-3-thiophen-2-yl-propionamide

HRID 1270991Notes

Reaction equation

HRID 1270991 reaction equation
C(O[C:6](=[O:26])[NH:7][C@H:8]([C:15](=[O:25])[NH:16][CH2:17][CH2:18][CH2:19][N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1)[CH2:9][C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)(C)(C)C.C(Cl)CCl.[CH:31]1[CH:32]=[CH:33][C:34]2[N:39](O)N=N[C:35]=2[CH:36]=1.C(OC(N[C@@H:49]([CH2:53][C:54]1S[CH:56]=[CH:57][CH:58]=1)C(O)=O)=O)(C)(C)C.N1(CCCN)CCCC1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[C:31]1([C:49]2[CH:53]=[CH:54][CH:58]=[CH:57][CH:56]=2)[CH:36]=[CH:35][C:34]([NH:39][C:6](=[O:26])[NH:7][C@@H:8]([CH2:9][C:10]2[S:11][CH:12]=[CH:13][CH:14]=2)[C:15]([NH:16][CH2:17][CH2:18][CH2:19][N:20]2[CH2:21][CH2:22][CH2:23][CH2:24]2)=[O:25])=[CH:33][CH:32]=1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 316701-PyrrolidinepropanamineHCID 757711-HydroxybenzotriazoleHCID 27344843-(Thien-2-yl)-L-alanine, N-BOC protectedHCID 69430524[(S)-1-(3-Pyrrolidin-1-yl-propylcarbamoyl)-2-thiophen-2-yl-ethyl]-carbamic acid tert-butyl ester

Product 1

HCID 11431495(S)-2-(3-Biphenyl-4-yl-ureido)-N-(3-pyrrolidin-1-yl-propyl)-3-thiophen-2-yl-propionamideYield 64%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

[(S)-1-(3-Pyrrolidin-1-yl-propylcarbamoyl)-2-thiophen-2-yl-ethyl]-carbamic acid tert-butyl ester. To a mixture of EDC (0.53 g, 2.77 mmol), HOBT (0.37 g, 2.77 mmol) and (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (0.5 g, 1.85 mmol) in DMF (10 mL), 3-pyrrolidin-1-yl-propylamine (3.85 g, 30 mmol) was added followed by N-methyl morpholine (0.37 g, 3.69 mmol) at rt. The solution was stirred for 15 h, diluted with EtOAc (150 mL), washed with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), and dried (Na2SO4). The solvent was removed, and the residue was stirred in a mixture of 10% EtOAc/hexanes at 0° C. for 0.5 h to afford 0.45 g (64%) of the desired product as a white solid. MS (electrospray): mass calculated for C19H14N3O3S, 381.21; m/z found, 382.2 [M+H]+, 404.2 [M+Na]+. 1H NMR (400 MHz, CD3OD): 7.22 (d, J=4.9 Hz, 1H), 6.93–6.87 (m, 2H), 4.22 (t, J=7.2 Hz, 1H), 3.31–3.09 (m, 4H), 2.54 (br m, 4H), 2.46 (t, J=7.6 Hz, 2H), 1.8 (br m, 4H), 1.67 (m, 2H), 1.41 (s, 9H).

Workup

  1. additionwas added
  2. washwashed with saturated NaHCO3 (2×50 mL) and brine (2×50 mL)
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was removed
  5. stirringthe residue was stirred in a mixture of 10% EtOAc/hexanes at 0° C. for 0.5 h

Sources & evidence

ORD record
ord-c04fc4d7ba2a4fb0b264c6a7db1085b3
Source dataset
uspto-grants-2007_04
Patent number
US07202269B2

Reaction notes

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