Trifluoroacetic acid → HCID 51035063, compound

HRID 593428Notes

Reaction equation

HRID 593428 reaction equation
[CH2:1]([NH:4][C:5]([C:7]1=[CH:8][C:9]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:33])=[CH:28][CH:27]=3)=[CH:22][C:10]=2[N:11]=[C:12]([NH:14]C(=O)OC(C)(C)C)[CH2:13]1)=[O:6])[CH2:2][CH3:3].FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:14][C:12]1[CH2:13][C:7]([C:5]([NH:4][CH2:1][CH2:2][CH3:3])=[O:6])=[CH:8][C:9]2[CH:25]=[CH:24][C:23]([C:26]3[CH:31]=[CH:30][C:29]([C:32]([N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:33])=[CH:28][CH:27]=3)=[CH:22][C:10]=2[N:11]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 86652677tert-butyl (1E,4E)-4-(propylcarbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate

Product 1

HCID 51035063HCID 51035063, compoundYield 7.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tert-butyl (1E,4E)-4-(propylcarbamoyl)-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepin-2-ylcarbamate (450 mg, 0.87 mmol) in CH2Cl2 (5 mL) was added 2,2,2-trifluoroacetic acid (1.36 mL, 17.4 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 2 h. The reaction mixture was concentrated under reduced pressure to give the crude material that was diluted with CH2Cl2 (10 mL) and sat'd aq NaHCO3 (15 mL) again. The resulting mixture was stirred for 30 min at room temperature. The aqueous layer was separated and extracted with CH2Cl2 (1×10 mL). The combined organic layers were washed with sat'd aq NaHCO3 (2×10 mL) and brine (1×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material again that was purified by silica gel flash column chromatography (1 to 5% MeOH in CH2Cl2, gradient) to yield 27 mg (7%) of (1E,4E)-2-amino-N-propyl-8-(4-(pyrrolidine-1-carbonyl)phenyl)-3H-benzo[b]azepine-4-carboxamide. MS APCI(+) m/z 417 (M+1) detected; 1H-NMR (400 MHz, d6-DMSO) δ 8.27 (t, 1H), 7.75 (d, 2H), 7.62 (d, 2H), 7.50 (d, 2H), 7.41 (d, 2H), 3.43-3.51 (m, 4H), 3.18 (q, 2H), 2.99 (s, 2H), 1.81-1.90 (m, 4H), 1.48-1.58 (m, 2H), 0.90 (t, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customto give the crude material that
  3. stirringThe resulting mixture was stirred for 30 min at room temperature
  4. customThe aqueous layer was separated
  5. extractionextracted with CH2Cl2 (1×10 mL)
  6. washThe combined organic layers were washed with sat'd aq NaHCO3 (2×10 mL) and brine (1×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude material again
  11. customthat was purified by silica gel flash column chromatography (1 to 5% MeOH in CH2Cl2, gradient)

Sources & evidence

ORD record
ord-a52e4980614647f6902e443ed1f71610
Source dataset
uspto-grants-2016_01
Patent number
US09242964B2

Reaction notes

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