Phenol → (S)-3-{4-Amino-2-[(R)-1-methyl-2-(2-methylsulfanyl-benzoimidazol-1-yl)-ethoxy]-benzenesulfonylamino-}4,4-diethoxy-butyric Acid Tert-Butyl Ester

HRID 1814389Notes

Reaction equation

HRID 1814389 reaction equation
[C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=1[OH:27])(=[O:19])=[O:18])[CH:9]([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])([CH3:4])([CH3:3])[CH3:2].[CH3:29][S:30][C:31]1[N:35]([CH2:36][C@@H:37](O)[CH3:38])[C:34]2[CH:40]=[CH:41][CH:42]=[CH:43][C:33]=2[N:32]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(O)C=CC=CC=1>C1COCC1.C(OCC)(=O)C.CCCCCCC>[C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=1[O:27][C@H:37]([CH3:38])[CH2:36][N:35]1[C:34]2[CH:40]=[CH:41][CH:42]=[CH:43][C:33]=2[N:32]=[C:31]1[S:30][CH3:29])(=[O:18])=[O:19])[CH:9]([O:10][CH2:11][CH3:12])[O:13][CH2:14][CH3:15])([CH3:3])([CH3:4])[CH3:2]

Participants

8

Reactant 5

HCID 996PhenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 69692264(S)-3-(4-amino-2-hydroxy-benzenesulfonylamino)-4,4-diethoxy-butyric acid tert-butyl esterHCID 69730043(2S)-1-[2-(methylsulfanyl)-1H-benzo[d]imidazol-1-yl]propan-2-ol

Product 1

HCID 69732105(S)-3-{4-Amino-2-[(R)-1-methyl-2-(2-methylsulfanyl-benzoimidazol-1-yl)-ethoxy]-benzenesulfonylamino-}4,4-diethoxy-butyric Acid Tert-Butyl Ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

To a 0° C. solution of (S)-3-(4-amino-2-hydroxy-benzenesulfonylamino)-4,4-diethoxy-butyric acid tert-butyl ester (200 mg, 0.48 mmol), (2S)-1-[2-(methylsulfanyl)-1H-benzo[d]imidazol-1-yl]propan-2-ol (150 mg, 0.67 mmol) and resin bound triphenyl phosphine (1 g, 1 mmol) in THF (5 mL) was added diisopropyl azodicarboxylate (600 uL, 3 mmol). This mixture was shaken at room temperature for 2 h. TLC 50% ethyl acetate/heptane shows no phenol rf 0.2. The reaction mixture was filtered, the resin was washed with dichloromethane, the organics were combined, the solvent was evaporated under reduced pressure. (S)-3-{4-amino-2-[(R)-1-methyl-2-(2-methylsulfanyl-benzoimidazol-1-yl)-ethoxy]-benzenesulfonylamino}-4,4-diethoxy-butyric acid tert-butyl ester was purified by silica gel chromatography ethyl acetate/heptane (132 mg, 44%). RP-HPLC (10 to 9O % acetonitrile in 0.1 N aqueous ammonium acetate over 10 min at 2 mL/min using a Waters Symmetry C18 150×4.6 mm column) 9.8 min.

Workup

  1. filtrationThe reaction mixture was filtered
  2. washthe resin was washed with dichloromethane
  3. customthe solvent was evaporated under reduced pressure
  4. custom(S)-3-{4-amino-2-[(R)-1-methyl-2-(2-methylsulfanyl-benzoimidazol-1-yl)-ethoxy]-benzenesulfonylamino}-4,4-diethoxy-butyric acid tert-butyl ester was purified by silica gel chromatography ethyl acetate/heptane (132 mg, 44%)
  5. waitRP-HPLC (10 to 9O % acetonitrile in 0.1 N aqueous ammonium acetate over 10 min at 2 mL/min using
  6. custom9.8 min.

Sources & evidence

ORD record
ord-368d99b7019141e092dee9762308194a
Source dataset
uspto-grants-2005_04
Patent number
US06875765B2

Reaction notes

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