4-Methylmorpholine → (2-{2-[2-(2-{2[5-(4-Chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylcarbamoyl]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethyl)-carbamic acid tert-butyl ester

HRID 1689570Notes

Reaction equation

HRID 1689570 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23]([OH:25])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[Cl:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]2[S:65][C:64]([NH2:66])=[N:63][C:62]=2[CH3:67])=[CH:57][C:56]=1[S:68]([CH3:71])(=[O:70])=[O:69]>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][C:23](=[O:25])[NH:66][C:64]1[S:65][C:61]([C:58]2[CH:59]=[CH:60][C:55]([Cl:54])=[C:56]([S:68]([CH3:71])(=[O:70])=[O:69])[CH:57]=2)=[C:62]([CH3:67])[N:63]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27560011-(((Tert-butoxy)carbonyl)amino)-3,6,9,12-tetraoxapentadecan-15-oic acidHCID 578311165-[4-Chloro-3-(methylsulfonyl)phenyl]-4-methyl-1,3-thiazol-2-amine

Product 1

HCID 86639506(2-{2-[2-(2-{2[5-(4-Chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylcarbamoyl]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(2-{2-[2-(2-tert-butoxycarbonylamino-ethoxy)-ethoxy]-ethoxy}-ethoxy)-propionic acid (690 mg 1.9 mmol), EDAC (403 mg 2.1 mmol), HOBT (284 mg 2.1 mmol), NMM (420 uL 3.8 mmol) and 5-(4-chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylamine (520 mg 1.7 mmol) were combined in dimethylformamide (16 ml) and stirred over night at room temperature. The solvent was removed under reduced pressure and the residue dissolved in dichloromethane (150 ml), washed with 1M HCl aqueous solution (50 ml) and saturated aqueous sodium hydrogen carbonate (50 ml), dried (Magnesium sulphate), filtered and evaporated. The residue was purified by flash chromatography using 50 g IST silica flash cartridge eluting with 0-2% methanol/dichloromethane to yield (2-{2-[2-(2-{2[5-(4-chloro-3-methanesulfonyl-phenyl)-4-methyl-thiazol-2-ylcarbamoyl]-ethoxy}-ethoxy)-ethoxy]-ethoxy}-ethyl)-carbamic acid tert-butyl ester as an oil (1.1 g residual solvent present) 1H NMR (400 MHz CDCl3) 10.3 (br s, 1H), 8.2 (s, 1H), 7.6 (m, 2H), 7.2 (br s, 1H), 3.9 (t, 2H) 3.8-3.5 (br m, 14H), 3.3 (br m, 5H), 2.8 (t, 2H), 2.4 (s, 3H), 1.4 (s, 9H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue dissolved in dichloromethane (150 ml)
  3. washwashed with 1M HCl aqueous solution (50 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)
  4. dry with materialdried (Magnesium sulphate)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 0-2% methanol/dichloromethane

Sources & evidence

ORD record
ord-7f97a4e80b7d45339cf9a56dc7b69b8c
Source dataset
uspto-grants-2012_04
Patent number
US08153389B2

Reaction notes

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