Ammonium Chloride → HCID 68283157, compound

HRID 1527541Notes

Reaction equation

HRID 1527541 reaction equation
[O:1]=[C:2]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21](=[O:34])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:33])([F:32])[F:31])[CH:24]=1)[CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13](O)=[O:14])=[CH:5]1.C1C[N:38]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-].C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[O:1]=[C:2]([N:16]1[CH2:20][CH2:19][CH2:18][C@H:17]1[C:21](=[O:34])[NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][C:30]([F:32])([F:31])[F:33])[CH:24]=1)[CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([NH2:38])=[O:14])=[CH:5]1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2724699PyBOPHCID 68284484HCID 68284484, compound

Product 1

HCID 68283157HCID 68283157, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-{2-oxo-2-[(S)-2-(3-trifluoromethoxy-phenylcarbamoyl)-pyrrolidin-1-yl]-ethyl}-1H-indole-3-carboxylic acid (11 mg, 0.023 mmol), was treated with PyBOP (12 mg, 0.023 mmol), HOBt (3.54 mg, 0.023 mmol), DIPEA (16 μL, 0.092 mmol), and NH4Cl (1 mg, 0.069 mmol) in DMF (1 mL) and the reaction mixture was stirred at RT under nitrogen for 3 h, then poured into an aqueous saturated solution of NaHCO3, EtOAc (20 mL) was added and the layers were separated. The aqueous layer was back-extracted twice with EtOAc and the combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min) to give after lyophilization of the purified fractions the desired compound. TLC, Rf (CH2Cl2/MeOH 95:5)=0.17; MS (LC/MS): 473.2 [M−H]−; tR (HPLC conditions a): 3.24 min.

Workup

  1. additionwas added
  2. customthe layers were separated
  3. extractionThe aqueous layer was back-extracted twice with EtOAc
  4. dry with materialthe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by preparative HPLC (Waters SunFire C18-ODB, 5 μm, 19×50 mm, 20% CH3CN/H2O 2.5 min, 20-100% CH3CN/H2O in 10 min, CH3CN/H2O containing 0.1% HCOOH flow: 20 mL/min)
  8. customto give after lyophilization of the
  9. custompurified fractions the desired compound
  10. custom3.24 min.

Sources & evidence

ORD record
ord-fe95dd5cd04742e4b991c873516a077d
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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