Trifluoroacetic acid → HCID 68830708, compound

HRID 1988067Notes

Reaction equation

HRID 1988067 reaction equation
[NH2:1][C:2]([C:4]1[CH:8]=[C:7]([C:9]2[CH:33]=[CH:32][CH:31]=[CH:30][C:10]=2[O:11][CH2:12][CH2:13][N:14]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)C(=O)OC(C)(C)C)[S:6][C:5]=1[NH:34][C:35]([NH2:37])=[O:36])=[O:3].FC(F)(F)C(O)=O>>[NH2:37][C:35]([NH:34][C:5]1[S:6][C:7]([C:9]2[CH:33]=[CH:32][CH:31]=[CH:30][C:10]=2[O:11][CH2:12][CH2:13][NH:14][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)=[CH:8][C:4]=1[C:2]([NH2:1])=[O:3])=[O:36]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68828137HCID 68828137, compound

Product 1

HCID 68830708HCID 68830708, compound

Procedure

The title compound was prepared by treating tert-butyl N-[2-(2-{3-(aminocarbonyl)-2-[(aminocarbonyl)amino]thien-5-yl}phenoxy)ethyl]-N-[4-fluorobenzyl]carbamate with 10% aqueous trifluoroacetic acid for 2 h at ambient temperature followed by purification using cation exchange chromatography. MS (ES) 429 (M+H)+. 1H NMR (DMSO-D6) 2.9 (m, 2H), 3.8 (s, 2H), 4.15 (m, 2H), 6.85 (br, 2H), 6.95 (m, 1H), 7.05 (m, 3H), 7.2 (m, 2H), 7.35 (m, 2H), 7.6 (m, 2H), 7.75 (s, 1H), 10.92 (s, 1H). b) tert-Butyl N-[2-(2-{3-(aminocarbonyl)-2-[(aminocarbonyl)amino]thien-5-yl)phenoxy)ethyl]-N-[4-fluorobenzyl]carbamate The title compound was prepared from tert-butyl N-[2-(2-bromophenoxy)ethyl]-N-[4-fluorobenzyl]carbamate in a similar manner to Example 1 (a) except that the concentrated reaction mixture was partitioned between DCM and saturated sodium carbonate. The solvent layer was washed (brine), dried and evaporated to leave an oil. The pure product was obtained by silica chromatography eluting with DCM/methanol mixtures. MS (ES) 529 (M+H)+. 1H NMR (DMSO-D6) 1.35 (s, 9H), 3.6 (m, 2H), 4.1 (m, 2H), 4.4 (m, 2H), 6.8 (m, 2H), 7.1 (m, 2H), 7.25 (m, 3H), 7.6 (m, 6H), 10.98 (s, 1H). c) tert-Butyl N-[2-(2-bromophenoxy)ethyl]-N-[4-fluorobenzyl]carbamate A solution of di-tert-butyl dicarbonate (1.86 g) in DCM (5 ml) was added over 5 min to a stirred solution of N-[2-(2-bromophenoxy)ethyl]-N-[4-fluorobenzyl]amine (2.5 g) in DCM (20 ml) and the resulting mixture was stirred at room temperature for 4 h. The reaction was diluted with DCM and then washed with water. After drying, the solvent was evaporated to yield an oil (2.9 g). MS (ES) 424 (M+H)+. d) N-[2-(2-Bromophenoxy)ethyl]-N-[4-fluorobenzyl]amine The title compound was prepared from 1-bromo-2-(2-chloroethoxy)benzene and 4-fluorobenzylamine in a similar manner to Example 1 (b). MS (ES) 324 (M+H)+.

Workup

  1. customfollowed by purification
  2. customwas partitioned between DCM and saturated sodium carbonate
  3. washThe solvent layer was washed (brine)
  4. customdried
  5. customevaporated
  6. customto leave an oil
  7. customThe pure product was obtained by silica chromatography
  8. washeluting with DCM/methanol mixtures
  9. additionc) tert-Butyl N-[2-(2-bromophenoxy)ethyl]-N-[4-fluorobenzyl]carbamate A solution of di-tert-butyl dicarbonate (1.86 g) in DCM (5 ml) was added over 5 min to a stirred solution of N-[2-(2-bromophenoxy)ethyl]-N-[4-fluorobenzyl]amine (2.5 g) in DCM (20 ml)
  10. additionThe reaction was diluted with DCM
  11. washwashed with water
  12. customAfter drying
  13. customthe solvent was evaporated

Sources & evidence

ORD record
ord-85d983e0c9c94fd79f14bc3202bd4451
Source dataset
uspto-grants-2009_06
Patent number
US07553868B2

Reaction notes

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