Sodium Sulfate → HCID 67464623, compound

HRID 1476967Notes

Reaction equation

HRID 1476967 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[C:16]([CH3:34])=[CH:17][N:18]([CH:31]([CH3:33])[CH3:32])[C:19]=2[CH:20]=[C:21]([C:23]2[CH:24]=[N:25][C:26]([CH:29]=O)=[CH:27][CH:28]=2)[CH:22]=1)=[O:13].[NH:35]1[CH2:39][CH2:38][CH2:37][CH2:36]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[C:16]([CH3:34])=[CH:17][N:18]([CH:31]([CH3:33])[CH3:32])[C:19]=2[CH:20]=[C:21]([C:23]2[CH:24]=[N:25][C:26]([CH2:29][N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[CH:27][CH:28]=2)[CH:22]=1)=[O:13]

Participants

7

Reactant 4

HCID 24436Sodium SulfateHCID 31268PyrrolidineHCID 4311764Sodium borohydrideHCID 54670907N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(6-formylpyridin-3-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide

Product 1

HCID 67464623HCID 67464623, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(6-formylpyridin-3-yl)-1-isopropyl-3-methyl-1H-indole-4-carboxamide (100 mg, 0.219 mmol), in DCM (10 mL) and methanol (2 mL) was added pyrrolidine (0.035 mL, 0.438 mmol), followed by sodium sulfate (31.1 mg, 0.219 mmol). The reaction stirred at rt for 12 h, at which time sodium borohydride (16.57 mg, 0.438 mmol) was added and the reaction stirred rt for 2 h and 45° C. for 2 h. The reaction was quenched with water and extracted with EtOAc. The organic layer was evaporated. Purification by reverse phase Gilson HPLC (10-60% acetonitrile/water+0.1% TFA, YMC ODS-A C18 Column 75×30 mm ID S-5 um, 12 nM Column 7 minutes), followed by isolation and extraction with EtOAc/0.1 N NaOH provided N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-3-methyl-6-(6-(pyrrolidin-1-ylmethyl)pyridin-3-yl)-1H-indole-4-carboxamide, which was evaporated from the organic layer as a yellow foam solid (68 mg, 0.125 mmol, 57.0% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.48 (br. s., 1H) 9.06 (d, J=2.02 Hz, 1H) 8.30 (dd, J=8.08, 2.27 Hz, 1H) 8.20 (t, J=5.18 Hz, 1H) 7.94 (d, J=1.26 Hz, 1H) 7.60 (d, J=8.08 Hz, 1H) 7.40 (s, 1H) 7.32 (s, 1H) 5.88 (s, 1H) 4.92-4.89 (m, 1H) 4.59 (d, J=5.56 Hz, 2H) 4.36 (d, J=5.05 Hz, 2H) 3.34 (br. s., 4H) 2.25 (s, 3H) 2.17 (d, J=1.01 Hz, 3H) 2.11 (s, 3H) 1.99 (br.s., 4H) 1.45 (d, J=6.57 Hz, 6H). LCMS: [M+H]+=512.3.

Workup

  1. additionwas added
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. customThe organic layer was evaporated
  5. customPurification by reverse phase Gilson HPLC (10-60% acetonitrile/water+0.1% TFA, YMC ODS-A C18 Column 75×30 mm ID S-5 um, 12 nM Column 7 minutes)
  6. extractionfollowed by isolation and extraction with EtOAc/0.1 N NaOH

Sources & evidence

ORD record
ord-4ee17772231c43549c810718d2e596fa
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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