Trifluoroacetic acid → HCID 52935024, compound

HRID 2366962Notes

Reaction equation

HRID 2366962 reaction equation
[N:1]1([C:7](OC(C)(C)C)=O)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:14][CH:15]([O:17][C:18](=[O:41])[NH:19][C@H:20]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([C:30]3[S:31][C:32](C=O)=[CH:33][N:34]=3)[CH:28]=2)[N:23]([C:37](=[O:39])[CH3:38])[C@@H:22]([CH3:40])[CH2:21]1)[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>ClCCl>[C:37]([N:23]1[C:24]2[C:29](=[CH:28][C:27]([C:30]3[S:31][C:32]([CH2:7][N:1]4[CH2:2][CH2:3][NH:4][CH2:5][CH2:6]4)=[CH:33][N:34]=3)=[CH:26][CH:25]=2)[C@H:20]([NH:19][C:18](=[O:41])[O:17][CH:15]([CH3:14])[CH3:16])[CH2:21][C@@H:22]1[CH3:40])(=[O:39])[CH3:38]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 86669240HCID 86669240, compound

Product 1

HCID 52935024HCID 52935024, compoundYield 57.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1,1-Dimethylethyl 1-piperazinecarboxylate (48.2 mg, 0.259 mmol), 1-methylethyl[(2S,4R)-1-acetyl-6-(5-formyl-1,3-thiazol-2-yl)-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Intermediate 106) (104 mg, 0.259 mmol) and sodium triacetoxyborohydride (220 mg, 1.036 mmol) were dissolved in dichloromethane (DCM) (4 mL) and the resulting mixture was stirred at room temperature under nitrogen for 16 h before being treated with a saturated NaHCO3 aqueous solution. The two layers were separated using a phase separator cartridge and the organic phase was concentrated in vacuo. The residue was loaded on a 20 G SCX cartridge which was eluted with MeOH then with a 2M NH3 solution in MeOH. The ammonia fractions were concentrated in vacuo to give a residue which was dissolved in DCM (3 mL) and treated with TFA (0.5 mL, 6.49 mmol). After 1 h, the mixture was concentrated in vacuo. Purification of the residue by flash chromatography on silica gel (gradient: 1 to 10% (2M NH3 in MeOH) in DCM) gave 1-methylethyl {(2S,4R)-1-acetyl-2-methyl-6-[5-(1-piperazinyl methyl)-1,3-thiazol-2-yl]-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (70 mg, 0.148 mmol, 57.3% yield).

Workup

  1. customThe two layers were separated
  2. concentrationthe organic phase was concentrated in vacuo
  3. washwas eluted with MeOH
  4. concentrationThe ammonia fractions were concentrated in vacuo
  5. customto give a residue which
  6. waitAfter 1 h
  7. concentrationthe mixture was concentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel (gradient: 1 to 10% (2M NH3 in MeOH) in DCM)

Sources & evidence

ORD record
ord-297d68330f1b442daea0f8ba7487a8a1
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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