Hydrochloric Acid → HCID 178426094, compound

HRID 1401896Notes

Reaction equation

HRID 1401896 reaction equation
[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][C:14]([C@H:17]([C:28](=[O:44])[NH:29][C:30]3[CH:35]=[CH:34][C:33]([C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=4[CH3:43])=[CH:32][CH:31]=3)[CH2:18][C:19]3[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=3)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH2:66][CH2:67][CH2:68][S:69]([OH:72])(=[O:71])=[O:70].CCN(C(C)C)C(C)C.Cl>CN(C=O)C.CCOC(C)=O.O>[C:1]([C@@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:12]=[CH:13][C:14]([C@H:17]([C:28](=[O:44])[NH:29][C:30]3[CH:35]=[CH:34][C:33]([C:36]4[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=4[CH3:43])=[CH:32][CH:31]=3)[CH2:18][C:19]3[CH:27]=[CH:26][C:22]([C:23]([NH:66][CH2:67][CH2:68][S:69]([OH:72])(=[O:71])=[O:70])=[O:25])=[CH:21][CH:20]=3)=[CH:15][CH:16]=2)[CH2:7][CH2:6]1)([CH3:2])([CH3:4])[CH3:3]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 1123TaurineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 178426095HCID 178426095, compound

Product 1

HCID 178426094HCID 178426094, compoundYield 36%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(R)-4-[2-(4-(4-(cis)-tert-Butyl-cyclohexyl)-phenyl]-2-(4′-chloro-2′-methyl-biphenyl-4-ylcarbamoyl)-ethyl]-benzoic acid (350 mg, 0.6 mmol), was taken up in 3 mL of DMF, followed by addition of HOBt (133 mg, 0.9 mmol), EDCI (132 mg, 0.7 mmol), taurine (86 mg, 0.7 mmol) and Hunig's base (374 mg, 2.9 mmol). The resulting reaction mixture was then stirred for 16 h at room temperature. The reaction solution was diluted with EtOAc (25 mL) and 10 mL of water, acidified with 2.4 N HCl. The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The organic extracts were combined, dried with Na2SO4, filtered through a frit and concentrated under reduced pressure to give a foam. The material was subjected to reverse phase HPLC purification to give the desired product as a white solid (150 mg, 36%). 1H NMR (CD3OD): δ 0.89 (9H, s), 1.10-1.60 (6H, m), 1.80-1.90 (4H, m), 2.38 (3H, s), 2.32-2.53 (1H, m), 3.05-3.10 (4H, m), 3.47-3.55 (1 h. dd), 3.77 (2H, t), 3.93-3.98 (1H, m), 7.09-7.47 (1H, m), 7.50 (2H, d), 7.70 (2H, d). Anal. Calcd. For C42H47ClN2O5S+NH3+1.2 H2O; C=65.22; H=7.13; N=5.57. Found C=65.31; H=7.00; N=5.57.

Workup

  1. customThe resulting reaction mixture
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered through a frit
  6. concentrationconcentrated under reduced pressure
  7. customto give a foam
  8. customphase HPLC purification

Sources & evidence

ORD record
ord-e97d598e837344e89c5681f6035de318
Source dataset
uspto-grants-2014_12
Patent number
US08907103B2

Reaction notes

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