Trifluoroacetic acid → HCID 67347140, compound

HRID 1676317Notes

Reaction equation

HRID 1676317 reaction equation
[C:1]([C:4]1([C:7]([NH:9][C:10]2[CH:40]=[CH:39][C:13]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]#[C:25][CH:26]5[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]5)[S:23][C:16]=34)=[C:12]([F:41])[CH:11]=2)=[O:8])[CH2:6][CH2:5]1)(=[O:3])[NH2:2].F[C:43]([F:48])(F)[C:44](O)=O>>[F:41][C:12]1[CH:11]=[C:10]([N:9]([C:4]2[CH:5]=[CH:6][C:43]([F:48])=[CH:44][CH:1]=2)[C:7]([C:4]2([C:1]([NH2:2])=[O:3])[CH2:6][CH2:5]2)=[O:8])[CH:40]=[CH:39][C:13]=1[O:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]2[CH:21]=[C:22]([C:24]#[C:25][CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)[S:23][C:16]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67347390HCID 67347390, compound

Product 1

HCID 67347140HCID 67347140, compoundYield 117.6%

Procedure

A mixture of tert-butyl 4-(2-(7-(4-(1-(carbamoyl)cyclopropanecarboxamido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)ethynyl)piperidine-1-carboxylate (Example 124, Step B, 20 mg, 0.0297 mmol) and 2,2,2-trifluoroacetic acid (339 mg, 2.97 mmol) were stirred at room temperature for 30 minutes. The reaction was concentrated in vacuo, using toluene to azeotrope (3×5 mL). The residue was partioned between EtOAc (5 mL) and 1:1 water/saturated aqueous NaHCO3 (5 mL). The phases were separated and the aqueous phase was re-extracted with EtOAc (2×5 mL). The combined organic phases were washed with brine (5 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The product was purified by preparative TLC (0.5 mm thickness, Rf=0.22), eluting with 10% MeOH (containing 7N NH3) in CHCl3. The product was obtained as a beige powder (10 mg, 55%). HPLC: 93% purity (220 nm); LRMS (APCI+): 94% purity, 220 nm, m/z 573 (M+1) detected; 1H NMR (400 MHz, CDCl3) δ 10.07 (s, 1H), 8.47 (d, J=6 Hz, 1H), 8.30 (s, 1H), 7.76 (m, 1H), 7.52 (s, 1H), 7.44 (m, 2H), 7.24 (m, 2H), 7.06 (t, J=9 Hz, 2H), 6.51 (d, J=6 Hz, 1H), 3.12 (m, 3H), 2.79 (m, 3H), 2.00 (m, 2H), 1.80 (m, 4H), 1.62 (m, 2H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc (2×5 mL)
  4. washThe combined organic phases were washed with brine (5 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe product was purified by preparative TLC (0.5 mm thickness, Rf=0.22)
  9. washeluting with 10% MeOH (containing 7N NH3) in CHCl3

Sources & evidence

ORD record
ord-cd87509e36dc47f7aa3f8881b04a46e2
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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