Methylamine → 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{5-[(methylamino)methyl]-2-thienyl}-1H-indole-7-carboxamide

HRID 562108Notes

Reaction equation

HRID 562108 reaction equation
[CH2:1]([S:3]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:28]([NH2:30])=[O:29])[CH:17]=[C:18]([C:21]4[S:22][C:23]([CH:26]=O)=[CH:24][CH:25]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])=[O:4])[CH3:2].[CH3:31][NH2:32].C1COCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CS(C)=O.C(O)(=O)C>[CH2:1]([S:3]([N:6]1[CH2:7][CH2:8][CH:9]([C:12]2[C:20]3[C:15](=[C:16]([C:28]([NH2:30])=[O:29])[CH:17]=[C:18]([C:21]4[S:22][C:23]([CH2:26][NH:32][CH3:31])=[CH:24][CH:25]=4)[CH:19]=3)[NH:14][CH:13]=2)[CH2:10][CH2:11]1)(=[O:4])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 577326703-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-2-thienyl)-1H-indole-7-carboxamide

Product 1

HCID 426290303-[1-(ethylsulfonyl)-4-piperidinyl]-5-{5-[(methylamino)methyl]-2-thienyl}-1H-indole-7-carboxamideYield 20%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-(5-formyl-2-thienyl)-1H-indole-7-carboxamide (35 mg, 0.078 mmol) in DMSO (1.0 mL) was added acetic acid (3 drops), 2 M methylamine in THF (0.24 mL, 0.471 mmol), and reacted for 3 h. Sodium triacetoxyborohydride (100 mg, 0.471 mmol) was then added and reaction was stirred overnight. All solvent was removed in vacuo and purified by Gilson Preparatory HPLC. The impure desired fraction was concentrated under reduced pressure and loaded onto a 500 mg SCX SPE cartridge primed with 10 mL of methanol. The cartridge was then sequentially eluted with 2M NH3 in MeOH (10 mL×2). The NH3 in MeOH fractions were concentrated to give 7.3 mg of the title compound (20%).

Workup

  1. customreacted for 3 h
  2. customreaction
  3. customAll solvent was removed in vacuo
  4. custompurified by Gilson Preparatory HPLC
  5. concentrationThe impure desired fraction was concentrated under reduced pressure
  6. washThe cartridge was then sequentially eluted with 2M NH3 in MeOH (10 mL×2)
  7. concentrationThe NH3 in MeOH fractions were concentrated

Sources & evidence

ORD record
ord-6ce5b01a3de044aba45fae176d86bb64
Source dataset
uspto-grants-2011_11
Patent number
US08063071B2

Reaction notes

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