Trifluoroacetic acid → HCID 59232142, compound

HRID 1099303Notes

Reaction equation

HRID 1099303 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:24]3[CH:29]=[C:28]([F:30])[C:27]([NH:31][C:32]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=4[F:45])=[O:33])=[CH:26][C:25]=3[F:46])[CH:9]=[C:10]([CH:11]3[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O.C(OCC)(=O)C>ClCCCl>[NH2:1][C:2]1[C:7]2=[C:8]([C:24]3[C:25]([F:46])=[CH:26][C:27]([NH:31][C:32]([NH:34][C:35]4[CH:40]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:38]=[CH:37][C:36]=4[F:45])=[O:33])=[C:28]([F:30])[CH:29]=3)[CH:9]=[C:10]([CH:11]3[CH2:12][CH2:13][NH:14][CH2:15][CH2:16]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 59232010HCID 59232010, compound

Product 1

HCID 59232142HCID 59232142, compoundYield 42.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A suspension of Example 274 (498 mg, 0.77 mmol) in 10 mL 1,2-dichloroethane was treated with 3 mL TFA at rt. The reaction quickly became homogeneous and at 10 min no starting material remained by RP-HPLC. The reaction mixture was concentrated in vacuo, and the residue taken up again in fresh 1,2-dichloroethane and concentrated again; this was repeated 2 times. The residue was taken up in THF (5 mL) and EtOAc (35 mL) and washed with aq. sodium carbonate. The organic layer was dried with sodium sulfate and concentrated in vacuo to provide a tan solid. Trituration with ethyl acetate provided the title compound (178 mg, 42%) as a tan solid. Concentration of the mother liquor provided an additional the title compound (201 mg, 48 mmol) of similar purity. 1H-NMR (DMSO-d6) δ 9.54 (bs, 2H), 8.70 (dd, 1H), 8.21 (dd, 1H), 7.96 (s, 1H), 7.60 (dd, 1H), 7.30-7.46 (m, 1H), 7.38 (dd, 1H), 6.57 (s, 1H), 3.16-3.31 (m, 1H), 3.02-3.12 (m, 2H), 2.60-2.74 (m, 2H), 1.89-2.02 (m, 2H), 1.60 (ddd, 2H), 1.42 (s, 9H); MS [M+H]+=550.2; LCMS RT=2.43

Workup

  1. customThe reaction quickly became homogeneous
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. concentrationconcentrated again
  4. washEtOAc (35 mL) and washed with aq. sodium carbonate
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto provide a tan solid

Sources & evidence

ORD record
ord-b80d65abf5b642a0acd949b033408104
Source dataset
uspto-grants-2012_03
Patent number
US08143393B2

Reaction notes

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