Methanol → HCID 11352196, compound

HRID 1243799Notes

Reaction equation

HRID 1243799 reaction equation
[C:1]([CH2:4][S:5][C:6]1[N:11]=[C:10](OS(C(F)(F)F)(=O)=O)[CH:9]=[C:8]([CH2:20][CH2:21][CH3:22])[C:7]=1[C:23]#[N:24])(=[O:3])[NH2:2].Cl.Cl.Cl.[NH:28]1[CH2:33][CH2:32][CH:31]([NH:34][CH2:35][CH:36]([OH:45])[CH2:37][O:38][C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)[CH2:30][CH2:29]1.C[O-].[Na+].CO>CN(C=O)C>[NH2:24][C:23]1[C:7]2[C:6](=[N:11][C:10]([N:28]3[CH2:33][CH2:32][CH:31]([NH:34][CH2:35][CH:36]([OH:45])[CH2:37][O:38][C:39]4[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=4)[CH2:30][CH2:29]3)=[CH:9][C:8]=2[CH2:20][CH2:21][CH3:22])[S:5][C:4]=1[C:1]([NH2:2])=[O:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 21928150HCID 21928150, compoundHCID 23400897HCID 23400897, compound

Product 1

HCID 11352196HCID 11352196, compoundYield 28.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a sealed tube was added trifluoro-methanesulfonic acid 6-carbamoylmethylsulfanyl-5-cyano-4-propyl-pyridin-2-yl ester (66.7 mg, 0.174 mmol) in 4 mL of dry DMF, followed by the addition of 1-(piperidin-4-ylamino)-3-(pyridin-4-yloxy)-propan-2-ol trihydrochloride salt (69 mg, 0.191 mmol) and N-N-diisopropylethylamine (180 mg, 1.39 mmol). The reaction mixture was stirred at 70° C. for 2 h. DMF was removed in vacuo. The residue was dissolved in 5 mL of MeOH, followed by the addition of sodium methoxide, 0.5 M solution in MeOH (1.74 mL, 0.86 mmol). The reaction mixture was stirred at 70° C. for 2 h. The reaction mixture was concentrated in vacuo. The residue was loaded onto a flash chromatography column. The column was eluted with 0–5% 2M NH3 in MeOH/CH2Cl2. The product fractions were collected, concentrated and dried under high vacuum pump to afford 24 mg (28.5%) of the title compound as a light brown solid product. (TLC: Rf=0.4, 5% 2M NH3 in MeOH/CH2Cl2, UV). ES+ 485.29 m/z (MH+)

Workup

  1. customDMF was removed in vacuo
  2. dissolutionThe residue was dissolved in 5 mL of MeOH
  3. stirringThe reaction mixture was stirred at 70° C. for 2 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. washThe column was eluted with 0–5% 2M NH3 in MeOH/CH2Cl2
  6. customThe product fractions were collected
  7. concentrationconcentrated
  8. customdried under high vacuum pump

Sources & evidence

ORD record
ord-2d894139780449f7abc6eebca08daa08
Source dataset
uspto-grants-2006_10
Patent number
US07119102B2

Reaction notes

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