Water → HCID 10070150, compound

HRID 1988065Notes

Reaction equation

HRID 1988065 reaction equation
[NH2:1][C:2]([C:4]1[CH:8]=[C:7]([C:9]2[CH:32]=[CH:31][CH:30]=[CH:29][C:10]=2[O:11][CH2:12][CH2:13][N:14]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[S:6][C:5]=1[NH:33][C:34]([NH2:36])=[O:35])=[O:3].C1(SC)C=CC=CC=1.FC(F)(F)C(O)=O.O>C(Cl)Cl>[NH2:1][C:2]([C:4]1[CH:8]=[C:7]([C:9]2[CH:32]=[CH:31][CH:30]=[CH:29][C:10]=2[O:11][CH2:12][CH2:13][N:14]([CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[S:6][C:5]=1[NH:33][C:34]([NH2:36])=[O:35])=[O:3].[NH2:36][C:34]([NH:33][C:5]1[S:6][C:7]([C:9]2[CH:32]=[CH:31][CH:30]=[CH:29][C:10]=2[O:11][CH2:12][CH2:13][NH:14][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:8][C:4]=1[C:2]([NH2:1])=[O:3])=[O:35]

Participants

7

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 7520ThioanisoleHCID 86760892HCID 86760892, compound

Product 2

HCID 10070150HCID 10070150, compoundHCID 86760892HCID 86760892, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl N-[2-(2-{3-(aminocarbonyl)-2-[(aminocarbonyl)amino]thien-5-yl}phenoxy)ethyl]-N-benzylcarbamate (0.16 g) was dissolved in DCM (3 ml); thioanisole (0.5 g) and trifluoroacetic acid (1 ml) were added. The mixture was stirred for 30 min, then water (5 ml) was added and the mixture extracted with DCM. The DCM was added to a SCX cation exchange column and eluted with 30% methanol-DCM to remove the thioanisole, then with methanolic ammonia-DCM mixtures. The solvent was evaporated and the residue recrystallised from methanol affording the title compound as a white solid (0.04 g). MS (ES) 411 (M+H)+. 1H NMR (DMSO-D6) 2.9 (t, 2H), 3.8 (s, 2H), 4.1 (t, 2H), 6.9 (s, 2H), 7.0 (t, 1H), 7.05 (d, 1H), 7.15-7.35 (m, 8H), 7.6 (d, 1H), 7.65 (s, 1H), 7.8 (s, 1H), 10.9 (s, 1H). b) tert-Butyl N-[2-(2-{3-(aminocarbonyl)-2-[(aminocarbonyl)amino]thien-5-yl}phenoxy)ethyl]-N-benzylcarbamate This was prepared from tert-butyl N-benzyl-N-[2-(2-bromophenoxy)ethyl]carbamate in a similar manner to Example 1 (a), except that the DCM layer was chromatographed twice on silica in DCM-methanol mixtures affording the title compound as a resinous solid. MS (ES) 511 (M+H)+. 1H NMR (DMSO-D6) 1.35 (s, 9H), 3.6 (t, 2H), 4.2 (t, 2H), 4.5 (s, 2H), 6.5 (s 2H), 6.9-7.4 (m, 10H), 7.5 (d, 1H), 7.6 (s, 1H), 10.9 (s, 1H) c) tert-Butyl N-benzyl-N-[2-(2-bromo henoxy)ethyl]carbamate A solution of di-t-butyl dicarbonate (0.96 g) in DCM (4 ml) was added over 5 min to a stirred solution of N-benzyl-N-[2-(2-bromophenoxy)ethyl]amine (1.3 g) in DCM (16 ml) and the mixture was stirred for 1.5 h, then concentrated to 6 ml, and diluted with isohexane (12 ml). The solution was chromatographed on silica in isohexane-DCM mixtures affording the title compound as a colourless oil (0.9 g). MS (ES) 350 (M+H-56)+. 1H NMR (DMSO-D6, 100° C.) 1.4 (s, 9H), 3.5 (t, 2H), 4.15 (t, 2H), 4.55 (s, 2H), 6.9 (t, 1H), 7.1 (d, 1H), 7.2-7.35 (m, 6H), 7.55 (d, 1H). d) N-Benzyl-N-[2-(2-bromophenoxy)ethyl]amine This was prepared from benzylamine and 1-bromo-2-(2-chloroethoxy)benzene by the method of Example 1 (b). The material obtained after chromatography on silica in DCM-methanolic ammonia mixtures was stirred in DCM and a solid removed by filtration. Evaporation of the mother liquors afforded the title compound as an oil. 1H NMR (DMSO-D6) 2.9 (t, 2H), 3.2-3.3 (bs, 1H), 3.8 (s, 2H), 4.1 (t, 2H), 6.9 (t, 1H), 7.1 (d, 1H), 7.2-7.35 (m, 6H), 7.55 (d, 1H).

Workup

  1. extractionthe mixture extracted with DCM
  2. additionThe DCM was added to a SCX cation exchange column
  3. washeluted with 30% methanol-DCM
  4. customto remove the thioanisole
  5. customThe solvent was evaporated
  6. customthe residue recrystallised from methanol affording the title compound as a white solid (0.04 g)
  7. customwas chromatographed twice on silica in DCM-methanol mixtures

Sources & evidence

ORD record
ord-ed0058cb85d54149aa9373d30f38a67c
Source dataset
uspto-grants-2009_06
Patent number
US07553868B2

Reaction notes

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