Dimethylformamide → 3-Amino-6-{4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide

HRID 1243787Notes

Reaction equation

HRID 1243787 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH:16]([OH:27])[C:17]3[N:21]([CH3:22])[C:20]4[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=4[N:18]=3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([C:28]([F:31])([F:30])[F:29])[C:3]=1[C:32]#[N:33].CN(C=O)C.[SH:39][CH2:40][C:41]([NH2:43])=[O:42].C[O-].[Na+]>CO>[NH2:33][C:32]1[C:3]2[C:2](=[N:7][C:6]([N:8]3[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][CH:16]([OH:27])[C:17]4[N:21]([CH3:22])[C:20]5[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=5[N:18]=4)[CH2:10][CH2:9]3)=[CH:5][C:4]=2[C:28]([F:31])([F:30])[F:29])[S:39][C:40]=1[C:41]([NH2:43])=[O:42]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 129612-Mercaptoacetamide2×HCID 10942334Sodium MethoxideHCID 219281596'-Chloro-4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4'-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carbonitrile

Product 1

HCID 114667603-Amino-6-{4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-piperidin-1-yl}-4-trifluoromethyl-thieno[2,3-b]pyridine-2-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

6′-Chloro-4-[2-hydroxy-2-(1-methyl-1H-benzoimidazol-2-yl)-ethylamino]-4′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carbonitrile (344.0 mg, 0.718) mmol was dissolved into 2 mL of dry DMF. To this was added a 1.09 M MeOHic solution of mercaptoacetamide (1.00 mL, 1.09 mmol) and a 1 M solution of MeOHic NaOMe (2.87 mL, 2.87 mmol). The reaction mixture was heated at 60° C. for 2 h. LC-MS indicated complete conversion to the mercaptoacetamide adduct. The reaction was then heated at 80° C. overnight. The reaction mixture was concentrated on a rotary evaporator with heating to 70° C. to give a dark orange oil. The oil was dissolved into a minimal amount of MeOH, applied to a SIO2 column and eluted with 0–10% MeOH/CH2Cl2 and 0–10% MeOH/CH2Cl2-1% NH3) to give 213.7 mg, 55.8%, of the title compound. ES+ 534.3 m/z (MH+)

Workup

  1. temperatureThe reaction was then heated at 80° C. overnight
  2. concentrationThe reaction mixture was concentrated on a rotary evaporator
  3. temperaturewith heating to 70° C.
  4. customto give a dark orange oil
  5. washeluted with 0–10% MeOH/CH2Cl2 and 0–10% MeOH/CH2Cl2-1% NH3)
  6. customto give 213.7 mg, 55.8%

Sources & evidence

ORD record
ord-d7faba7884654a0a9f73afe58cfbeea7
Source dataset
uspto-grants-2006_10
Patent number
US07119102B2

Reaction notes

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