Dimethylformamide → HCID 68513610, compound

HRID 1868493Notes

Reaction equation

HRID 1868493 reaction equation
[N:1]1([CH:7]2[CH2:11][NH:10][CH2:9][CH:8]2[OH:12])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1.C(N([CH:29]([CH3:31])[CH3:30])CC)(C)C.CN([CH:35]=[O:36])C>CN(C1C=CN=CC=1)C>[Cl:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([N:4]2[CH2:3][CH2:2][N:1]([CH:7]3[CH:8]([OH:12])[CH2:9][N:10]([C:35]([C:30]4[CH:29]=[CH:31][C:14]([Cl:13])=[CH:15][CH:16]=4)=[O:36])[CH2:11]3)[CH2:6][CH2:5]2)=[O:19])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 85014-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 63701856HCID 63701856, compound

Product 1

HCID 68513610HCID 68513610, compound

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

3,4-Epoxypyrrolidine carbamate Wang resin (0.15 g, 0.18 mmol) was placed in a glass reaction vessel (4 mL). LiClO4 (57 mg, 3 eq.), N-Boc piperazine (186 mg, 5.5 eq.) and acetonitrile (2 mL) were added. The glass reactor was closed with a screw cap and the reaction mixture was heated at 80° C. for 43 h. The resin was transferred into syringes and washed with acetonitrile: H2O (1:1, 2×), DMF (3×), MeOH (3×), DMF (3×), and CH2Cl2 (5×). The BOC group was removed by treating the resin with 10% methyl sulfide in TFA (2 mL) for 1 hour. This solution was saved and later combined with a cleavage solution. The product was further cleaved from resin by shaking with a solution of TFA:CH2Cl2:H2O (2 mL of 70:30:1.5) for 2.5 h (2×). All the solutions were combined and condensed to afford 170 mg of crude 4-piperazin-1-yl-pyrrolidin-3-ol (bistrifluoroacetate salt, used without purification). The crude 4-piperazin-1-yl-pyrrolidin-3-ol was dissolved in DMF (dry, 2 mL). To this solution was added 4-chloro-benzoyl chloride (46 μL, 0.36 mmol), diisopropyl ethyl amine (620 μL, 3.6 mmol), and DMAP (2 mg). The solution was stirred at RT for 30 minutes, and then separated by preparative LC-MS to yield 16-mg of the title compound as the trifluoroacetate salt. ESIMS ([M+H]+): 448.3 (100).

Workup

  1. customseparated by preparative LC-MS

Sources & evidence

ORD record
ord-92e0bffbf1784c3c8a2382e1375a7da5
Source dataset
uspto-grants-2009_12
Patent number
US07635698B2

Reaction notes

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