Triethylamine → 1-(2-{[6-({6-[{3-([tert-Butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]-1,3-benzothiazol-2-yl}amino)hexanoyl](methyl)amino}ethyl)piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446600Notes

Reaction equation

HRID 446600 reaction equation
[C:1]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:28])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])[CH3:19])[CH2:12][CH2:11]1.Br[C:36]1[S:37][C:38]2[CH:44]=[C:43]([C:45]([N:47]([CH3:60])[CH2:48][CH2:49][CH2:50][N:51]([CH3:59])[C:52](=[O:58])[O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:46])[CH:42]=[CH:41][C:39]=2[N:40]=1.C(N(CC)CC)C>C(O)CCC>[C:1]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:28])[O:9][CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:27])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][NH:26][C:36]2[S:37][C:38]3[CH:44]=[C:43]([C:45](=[O:46])[N:47]([CH2:48][CH2:49][CH2:50][N:51]([C:52]([O:53][C:54]([CH3:56])([CH3:55])[CH3:57])=[O:58])[CH3:59])[CH3:60])[CH:42]=[CH:41][C:39]=3[N:40]=2)[CH3:19])[CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 666715721-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate2×HCID 86663477tert-Butyl (3-{[(2-bromo-1,3-benzothiazol-6-yl)carbonyl](methyl)amino}propyl)methylcarbamate

Product 1

HCID 867619181-(2-{[6-({6-[{3-([tert-Butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]-1,3-benzothiazol-2-yl}amino)hexanoyl](methyl)amino}ethyl)piperidin-4-yl biphenyl-2-ylcarbamateYield 64%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent2×

Procedure

The compound (133 mg, 0.298 mmol) obtained in Example 1a and the compound (132 mg, 0.298 mmol) obtained in Example 93b were dissolved in n-butanol (3 mL), triethylamine (62 μL, 0.447 mmol) was added, and the mixture was stirred with heating to reflux for 15 hours. A solution of the compound (133 mg, 0.298 mmol) obtained in Example 1a in n-butanol (2 mL) was added to the reaction mixture, and the mixture was further stirred with heating to reflux for 24 hours. Subsequently, triethylamine (62 μL, 0.447 mmol) was added to the reaction mixture, and the mixture was further stirred with heating to reflux for 24 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→50:1, v/v) to give the title compound (157 mg; yield, 64%) as a light yellow solid.

Workup

  1. temperaturewith heating
  2. temperatureto reflux for 15 hours
  3. stirringthe mixture was further stirred
  4. temperaturewith heating
  5. temperatureto reflux for 24 hours
  6. stirringthe mixture was further stirred
  7. temperaturewith heating
  8. temperatureto reflux for 24 hours
  9. customThe solvent was evaporated under reduced pressure
  10. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→50:1, v/v)

Sources & evidence

ORD record
ord-be6c74db76b04b6cb3a170f7d5dc6461
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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