Triethylamine → AX-9657

HRID 1360334Notes

Reaction equation

HRID 1360334 reaction equation
[CH2:1]([C:3]1[C:12]2[C:11](=[O:13])[O:10][C:9]([C:14]3[C:15](F)=[N:16][CH:17]=[CH:18][CH:19]=3)=[N:8][C:7]=2[CH:6]=[C:5]([O:21][CH3:22])[CH:4]=1)[CH3:2].C(N(CC)CC)C.[CH3:30][N:31]([CH3:37])[C@H:32]1[CH2:36][CH2:35][NH:34][CH2:33]1>O1CCOCC1>[CH3:30][N:31]([CH3:37])[C@H:32]1[CH2:36][CH2:35][N:34]([C:15]2[C:14]([C:9]3[O:10][C:11](=[O:13])[C:12]4[C:3]([CH2:1][CH3:2])=[CH:4][C:5]([O:21][CH3:22])=[CH:6][C:7]=4[N:8]=3)=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:33]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 57340965HCID 57340965, compound

Product 1

HCID 25205741AX-9657Yield 75.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of compound S (37.60 g, 125 mmol) and triethylamine (42 mL, 301 mmol) in anhydrous 1,4-dioxane (800 mL) was added dropwise (S)-(−)-3-(dimethylamino)-pyrrolidine (17.1 g, 150 mmol) at room temperature under Ar. The resulting mixture was stirred for 8 hours. The solution was concentrated, and diluted with water (200 mL) and EtOAc (50 mL). The resulting solution was basified to pH 9 with saturated sodium bicarbonate and then extracted with ethyl acetate (3×300 mL). The organic layers were combined and washed with water, brine, and dried over anhydrous Na2SO4 followed by the removal of EtOAc in vacuo. The crude product was purified by column chromatography (Chromatrex NH-DM2035, Fuji Sislysia Chemical Co. Ltd.) using a gradient of 20-25% ethyl acetate/hexanes to yield compound 132 (37.03 g, 73%) as a yellow amorphous solid.

Workup

  1. concentrationThe solution was concentrated
  2. additiondiluted with water (200 mL) and EtOAc (50 mL)
  3. extractionextracted with ethyl acetate (3×300 mL)
  4. washwashed with water, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customfollowed by the removal of EtOAc in vacuo
  7. customThe crude product was purified by column chromatography (Chromatrex NH-DM2035, Fuji Sislysia Chemical Co. Ltd.)

Sources & evidence

ORD record
ord-2b903beaa98841eaba4055a42594c3ec
Source dataset
uspto-grants-2011_02
Patent number
US07879846B2

Reaction notes

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