Phosphoric Acid → HCID 178518304, compound

HRID 2236814Notes

Reaction equation

HRID 2236814 reaction equation
C(OC([N:8]1[CH2:13][CH:12]=[CH:11][CH2:10][CH:9]1[C:14]1[CH:19]=[CH:18][C:17]([NH:20][CH:21]=[C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:32]4[CH:36]=[CH:35][S:34][CH:33]=4)[CH:30]=3)[C:25](=[O:37])[NH:24][C:23]2=[O:38])=[CH:16][CH:15]=1)=O)(C)(C)C.OP(O)(O)=O.CC#N.[OH-].[Na+]>C(Cl)Cl.O>[NH:8]1[CH2:13][CH:12]=[CH:11][CH2:10][CH:9]1[C:14]1[CH:15]=[CH:16][C:17]([NH:20][CH:21]=[C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([C:32]4[CH:36]=[CH:35][S:34][CH:33]=4)[CH:30]=3)[C:25](=[O:37])[NH:24][C:23]2=[O:38])=[CH:18][CH:19]=1

Participants

7

Reactant 4

HCID 1004Phosphoric AcidHCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 178451833HCID 178451833, compound

Product 1

HCID 178518304HCID 178518304, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

2-{4-[(1,3-Dioxo-6-thiophen-3-yl-2,3-dihydro-1H-isoquinolin-4-ylidenemethyl)-amino]-phenyl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (230 mg, ˜60-70% pure, ˜0.26-0.31 mmol) is mixed with H3PO4 (1 mL) in CH2Cl2 (1 mL) at room temperature. The resulting mixture is stirred until no starting material is detected by TLC. CH3CN and H2O and ice were then added to dilute the sample. The mixture is neutralized by NaOH and extracted with EtOAc. The EtOAc layer is washed with brine and dried. After removal of EtOAc, the residue is purified by flash chromatography to provide the title compound (80 mg, 78% for two steps). 1H NMR (400 MHz, DMSO) δ 12.53 (1H, d, J=12.8 Hz), 11.30 (1H, s), 9.02 (1H, d, J=12.4 Hz), 8.34 (1H, s), 8.21 (1H, s), 8.05 (1H, d, J=7.6 Hz), 7.44-7.85 (7H, m), 5.76-5.84 (2H, m), 3.77-3.81 (1H, m), 3.31-3.50 (2H, m), 2.09-2.21 (2H, m). MS (ESI): 428.1 (M+1)−1.

Workup

  1. additionto dilute the sample
  2. extractionextracted with EtOAc
  3. washThe EtOAc layer is washed with brine
  4. customdried
  5. customAfter removal of EtOAc
  6. customthe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-44fa5330d030486e87793cef03aa7263
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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