Dimethylformamide → 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1182170Notes

Reaction equation

HRID 1182170 reaction equation
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][NH:21][CH2:20]4)[CH2:14][CH2:13]3)[C:9]2=[O:30])=[CH:5][CH:4]=1.[CH:33]1([CH2:36][CH2:37]C(O)=O)[CH2:35][CH2:34]1.CC(C)N=C=NC(C)C.CN(C=[O:54])C>CN(C1C=CN=CC=1)C>[CH:33]1([CH2:36][C:37]([N:21]2[CH2:22][C@H:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@@H:19]([CH2:18][N:15]3[CH2:16][CH2:17][C:10]4([C:9](=[O:30])[N:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=5)[CH2:12][CH2:11]4)[CH2:13][CH2:14]3)[CH2:20]2)=[O:54])[CH2:34][CH2:35]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 27580133-Cyclopropylpropanoic acidHCID 114646642-(4-Methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one

Product 1

HCID 111915488-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-oneYield 72%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

To 100 mg (0.23 mmol) of 2-(4-methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one in DMF (1 mL) was added cyclopropylmethylacetic acid (39 mg, 0.311 mmol), DIC (31 μL, 0.311 mmol) and DMAP (8 mg, 0.065 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and purified by flash silica chromatography eluting first with ethyl acetate:hexanes (20%-100%) and then with methanol:dichloromethane (1:25) to give 116 mg (72%) of 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one. The compound was then dissolved in methanol (2 mL) and HCl (aq., 0.2M, 3 mL) and stirred for 10 minutes. The solvent was removed in vacuo, and the solution lyophilized to give the Compound 117 (120 mg, 95%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by flash silica chromatography
  3. washeluting first with ethyl acetate

Sources & evidence

ORD record
ord-1de0df9698c7460eb6b9b3dad3218d28
Source dataset
uspto-grants-2007_10
Patent number
US07288548B2

Reaction notes

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