Ammonium Chloride → (3-Carbamoyl-6-methoxy-indol-1-yl)-acetic acid tert-butyl ester

HRID 1527208Notes

Reaction equation

HRID 1527208 reaction equation
[C:1]([O:5][C:6]([CH2:8][N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11]([C:20]([OH:22])=O)=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-].C[N:26](C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6](=[O:7])[CH2:8][N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11]([C:20](=[O:22])[NH2:26])=[CH:10]1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 25517Ammonium Chloride2×HCID 81531Diisopropylethylamine2×HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682834641-tert-Butoxycarbonylmethyl-6-methoxy-1H-indole-3-carboxylic acid

Product 1

HCID 68283635(3-Carbamoyl-6-methoxy-indol-1-yl)-acetic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-tert-butoxycarbonylmethyl-6-methoxy-1H-indole-3-carboxylic acid (500 mg, 1.28 mmol) in DMF (6 mL) were added successively NH4Cl (137 mg, 2.55 mmol), HBTU (1.21 g, 3.19 mmol) and DIPEA (0.90 mL, 5.11 mmol), and stirring was continued at RT for 16 h. Additional aliquots of NH4Cl (2 equiv) and DIPEA (4 equiv) were added to the reaction mixture. After stirring for 16 h, water was added and the aqueous layer was extracted repeatedly with EtOAc. The combined organics were washed with saturated aqueous NaHCO3 solution and brine, dried (phase separator) and concentrated in vacuo. Purification by preparative HPLC (Macherey Nagel, VP250/40, C18 nucleosil 100-10, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) and lyophilization of the purified fractions afforded the title compound as a beige solid. MS: 305 [M+H]+, 609 [2M+H]+; tR (HPLC conditions c): 4.26 min.

Workup

  1. stirringAfter stirring for 16 h
  2. extractionthe aqueous layer was extracted repeatedly with EtOAc
  3. washThe combined organics were washed with saturated aqueous NaHCO3 solution and brine
  4. customdried (phase separator)
  5. concentrationconcentrated in vacuo
  6. customPurification by preparative HPLC (Macherey Nagel, VP250/40, C18 nucleosil 100-10, eluent: 20-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 mL/min) and lyophilization of the purified fractions

Sources & evidence

ORD record
ord-b6a26c497562407db2488b1e2456db2a
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…