HCID 66989160, compound → HCID 16733572, compound

HRID 473309Notes

Reaction equation

HRID 473309 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:37][CH:36]=1)[CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([NH:28][S:29]([CH3:32])(=[O:31])=[O:30])=[CH:24][CH:23]=1>CN>[NH2:3][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:37][CH:36]=1)[CH2:19][CH2:20][O:21][C:22]1[CH:23]=[CH:24][C:25]([NH:28][S:29]([CH3:32])(=[O:30])=[O:31])=[CH:26][CH:27]=1

Participants

3

Reactant 1

HCID 66989160HCID 66989160, compound

Product 1

HCID 16733572HCID 16733572, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 6329MethylamineSolvent

Procedure

Crude N-[4-({2-[[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl](2-{4-[(methylsulfonyl)amino]phenyl}ethyl)amino]ethyl}oxy)phenyl]methanesulfonamide (142 mg) was dissolved in methylamine (33% in ethanol, 10 ml, 0.216) and left at 22° C. for 48 h. Excess reagent was evaporated under reduced pressure and the oily residue azeotroped with two further portions of ethanol. The crude product was dissolved in acetonitrile/water/acetic acid (5/4/, <2 ml), half applied to a Phenomenex Jupiter C18 HPLC column and eluted using the following gradient (flow rate=10 ml/min, AU 20.0, 214 nm, AU 10, 256 nm, A=0.1% TFA/water, B=90% acetonitrile/10% water/0.1% TFA): t=0 min: B=5%; t=10 min: B=5%; t=100 min: B=35%; t=115 min: B=100%; t=130 min: B=100%. Fractions containing mainly the slower eluting component (>90%) were pooled and evaporated to give the title compound (14.9 mg). The remaining crude was applied to the C18 column but with a modified gradient: t=0 min: B=5%; t=10 min: B=5%; t=15 min: B=10%; t=95 min: B=30%; t=110 min: B=100%; t=125 min: B=100%. Fractions containing mainly the desired product were combined and evaporated as before to yield the title compound (21.3 mg˜80% purity). The material was used without further purification.

Workup

  1. customExcess reagent was evaporated under reduced pressure
  2. customthe oily residue azeotroped with two further portions of ethanol
  3. dissolutionThe crude product was dissolved in acetonitrile/water/acetic acid (5/4/, <2 ml)
  4. washeluted
  5. customt=0 min
  6. customt=10 min
  7. customt=100 min
  8. customt=115 min
  9. customt=130 min
  10. additionFractions containing mainly the
  11. washslower eluting component (>90%)
  12. customevaporated

Sources & evidence

ORD record
ord-977c56c5c4ec45ae9593b2fe1c56b922
Source dataset
uspto-grants-2014_01
Patent number
US08633319B2

Reaction notes

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