Trifluoroacetic acid → HCID 178483092, compound

HRID 1984945Notes

Reaction equation

HRID 1984945 reaction equation
C([O:5][C:6](=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15]2[N:24]=[C:23]([N:25]([CH3:27])[CH3:26])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]=2)[CH2:10][CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O.[F:36][C:37]1(C(O)=O)[CH:42]=[CH:41][C:40]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:39][CH2:38]1.C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:27][N:25]([CH3:26])[C:23]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([NH:14][C@H:11]2[CH2:12][CH2:13][C@H:8]([NH:7][C:6]([C:46]3[CH:45]=[CH:44][C:43]([C:40]4[CH:39]=[CH:38][C:37]([F:36])=[CH:42][CH:41]=4)=[CH:48][CH:47]=3)=[O:5])[CH2:9][CH2:10]2)[N:24]=1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66545360HCID 66545360, compoundHCID 178483095HCID 178483095, compound

Product 1

HCID 178483092HCID 178483092, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of trans-[4-(4-dimethlyamino-quinazolin-2-ylamino)-cyclohexyl]-carbamic acid tert-butyl ester (0.76 g, 0.20 mmol) in CH2Cl2 (20 mL) was added TFA (304 μL, 0.39 mmol). The solution was stirred at ambient temperature for 4 hr. The resulting mixture was concentrated and the residue was dissolved in CH2Cl2. The organic layer was washed with a dilute aqueous NaOH and aqueous NaHCO3 solution. The aqueous layer was extracted with CH2Cl2 (twice) and the organic layers combined, dried over MgSO4, and concentrated. To a solution of the residue (0.1 g) and 4-fluoro-biphenyl-4-carboxylic acid (76 mg, 0.35 mmol) in CH2Cl2 were added HOAt (62 mg, 0.46 mmol), WSC—HCl (87 mg, 0.46 mmol), and diisopropylethylamine (31 uL, 0.18 mmol). The mixture was stirred for 1 hr at ambient temperature and the reaction was quenched with water. The aqueous layer was extracted with CH2Cl2 (twice). The organic layers were combined, dried over MgSO4, concentrated and the residue purified by column chromatography (silica gel, 2% to 4% 2 M NH3/MeOH in CH2Cl2) to give trans-4′-fluoro-biphenyl-4-carboxylic acid [4-(4-dimethlyamino-quinazolin-2-ylamino)-cyclohexyl]-amide (35 mg, 0.072, 21%) as a white solid.

Workup

  1. concentrationThe resulting mixture was concentrated
  2. dissolutionthe residue was dissolved in CH2Cl2
  3. washThe organic layer was washed with a dilute aqueous NaOH and aqueous NaHCO3 solution
  4. extractionThe aqueous layer was extracted with CH2Cl2 (twice) and the organic layers
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. stirringThe mixture was stirred for 1 hr at ambient temperature
  8. customthe reaction was quenched with water
  9. extractionThe aqueous layer was extracted with CH2Cl2 (twice)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customthe residue purified by column chromatography (silica gel, 2% to 4% 2 M NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-25572b1a2e8244ecbb7e62bd3a8856be
Source dataset
uspto-grants-2009_06
Patent number
US07544690B2

Reaction notes

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