(3S)-(-)-3-(Dimethylamino)pyrrolidine → AX-9657

HRID 1360331Notes

Reaction equation

HRID 1360331 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].[CH3:23][N:24]([CH3:30])[C@H:25]1[CH2:29][CH2:28][NH:27][CH2:26]1>O1CCOCC1>[CH3:23][N:24]([CH3:30])[C@H:25]1[CH2:29][CH2:28][N:27]([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)[CH2:26]1

Participants

4

Reactant 2

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

Product 1

HCID 25205741AX-9657Yield 70%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of compound S (13.9 g, 46.4 mmol) in anhydrous 1,4-dioxane (232 mL) was treated with (S)-(−)-3-(dimethylamino)-pyrrolidine (7.50 mL, 60.3 mmol) at 100° C. under N2 for 10 minutes. The solution was concentrated, and the residue was purified using a Biotage 40M amine column using a gradient of 20-50% ethyl acetate/hexanes. The fractions containing compound 132 were combined and concentrated by rotary evaporation, dissolved in acetonitrile:water (1:1, 50 mL), and then lyophilized to afford compound 132 as a pale yellow powder (12.81 g, 70% yield). 1H NMR (CDCl3, 400 MHz) d: 8.30 (dd, 1H, J=1.5 Hz), 8.00 (dd, 1H, J=1.5 Hz), 6.95 (d, 1H, J=2.0 Hz), 6.88 (d, 1H, J=3.0 Hz), 6.72 (q, 1H, J=4.5 Hz), 3.92 (s, 3H), 3.66 (q, 1H, J=4.0 Hz), 3.48 (m, 3H), 3.21 (m, 2H), 2.78 (s, 1H), 2.26 (s, 6H), 2.12 (q, 1H, J=6.0 Hz), 1.84 (m, 1H), 1.29 (t, 3H, J=7.0 Hz); 13C NMR (CDCl3, 400 MHz) d: 165.5, 158.8, 158.1, 155.7, 151.1, 151.0, 150.6, 140.3, 117.9, 112.2, 110.6, 107.3, 107.1, 65.4, 55.9, 54.4, 49.1, 44.5, 30.3, 28.6, 15.2; ESMS m/z: 395.1 [M+H+]; Calculated for C22H26N4O3: C, 66.99; H, 6.64; N, 14.20. found: C, 66.81; H, 6.66; N, 14.14.

Workup

  1. concentrationThe solution was concentrated
  2. customthe residue was purified
  3. additionThe fractions containing compound 132
  4. concentrationconcentrated by rotary evaporation
  5. dissolutiondissolved in acetonitrile:water (1:1, 50 mL)

Sources & evidence

ORD record
ord-e2bd5d79c78e4d4ca92b7df807969635
Source dataset
uspto-grants-2011_02
Patent number
US07879846B2

Reaction notes

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