Trifluoroacetic acid → HCID 90404321, compound

HRID 1505668Notes

Reaction equation

HRID 1505668 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[C:20]([C:21](OCC)=[O:22])=[CH:19][N:18]=[C:17]3[S:26][C:27]([CH2:29][C:30]([F:33])([F:32])[F:31])=[CH:28][C:16]=23)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(C1C=C2C(=CC=1)NC(C#N)=C2)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CCOC(C)=O>[F:33][C:30]([F:31])([F:32])[CH2:29][C:27]1[S:26][C:17]2=[N:18][CH:19]=[C:20]([CH2:21][OH:22])[C:15]([NH:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10]3)=[C:16]2[CH:28]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 90404233HCID 90404233, compoundHCID 90404427HCID 90404427, compound

Product 1

HCID 90404321HCID 90404321, compoundYield 3.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 4-(1-(tert-butoxycarbonyl)piperidin-4-ylamino)-2-(2,2,2-trifluoroethyl)thieno[2,3-b]pyridine-5-carboxylate (45 mg, 0.1 mmol) was dissolved in CH2Cl2 (3 mL). Trifluoroacetic acid (2 mL) was added to the solution. After 2 hours, the solution was concentrated in vacuo. The residue was dissolved in CH2Cl2 (10 mL), and washed with a 10% solution of K2CO3 (2×1 mL), and dried over anhydrous K2CO3. The organic phase was concentrated to give tan residue, which was used in the next step without further purification. This residue was dissolved in 1,2-dichloroethane (1 mL). 5-formyl-1H-indole-2-carbonitrile (23 mg, 0.14 mmol) and sodium tri(acetoxy)borohydride (32 mg, 0.15 mmol) were added. The mixture was stirred at room temperature for 2 hours. The solution was diluted with EtOAc (10 mL) and washed with 0.1 N NaOH (1×5 mL). The organic phase was dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified by reversed-phase preparative HPLC (95:5-5:95 MeCN/H2O with 0.1% HCl buffer). The product containing fractions were lyophilized to afford the product as a white solid (1.4 mg, 2.5% yield), Compound 278. LC-MS: 1.45 min, 500.2 m/z [M+H]+.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. dissolutionThe residue was dissolved in CH2Cl2 (10 mL)
  3. washwashed with a 10% solution of K2CO3 (2×1 mL)
  4. dry with materialdried over anhydrous K2CO3
  5. concentrationThe organic phase was concentrated
  6. customto give tan residue, which
  7. customwas used in the next step without further purification
  8. dissolutionThis residue was dissolved in 1,2-dichloroethane (1 mL)
  9. washwashed with 0.1 N NaOH (1×5 mL)
  10. dry with materialThe organic phase was dried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was purified by reversed-phase preparative HPLC (95:5-5:95 MeCN/H2O with 0.1% HCl buffer)
  13. additionThe product containing fractions

Sources & evidence

ORD record
ord-835a85748f054ea0bf2daa697d25623f
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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