Sodium Hydroxide → HCID 86706712, compound

HRID 1476783Notes

Reaction equation

HRID 1476783 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]3[C:20](=[O:21])[C:19]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[C:7]=3[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1.ClC(=O)[C:24]([O:26]C)=[O:25].CN1C2C3C=CC=CC=3C(=O)C=2C2C(=CC(NC(=O)C(OC)=O)=CC=2)C1=O.[OH-].[Na+]>O1CCCC1.O.C(O)C.C(N(CC)CC)C>[CH3:13][N:8]1[C:7]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:20](=[O:21])[C:6]=2[C:5]2[C:10](=[CH:11][C:2]([NH:1][C:24](=[O:25])[OH:26])=[CH:3][CH:4]=2)[C:9]1=[O:12]

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 79846Methyl chloroglyoxylateHCID 71546175HCID 71546175, compoundHCID 86706713HCID 86706713, compound

Product 1

HCID 86706712HCID 86706712, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-6-methyl-5H-indeno[1,2-c]isoquinoline-5,11(6H)-dione (3, 201 mg, 0.72 mmol) was dissolved in tetrahydrofuran (30 mL) and cooled to 0° C. Methyl oxalyl chloride (4, 0.1 mL, 1.16 mmol) and triethylamine (0.2 mL) were added dropwise and the reaction mixture was stirred for 2 h at 0° C. The reaction mixture was diluted with water (100 mL) and extracted with chloroform (4×50 mL). The solvent was removed under vacuum and the compound passed through a short silica gel column chromatography, eluting with chloroform-methanol, 9:1. The impure solid, compound 9, was dissolved in a solution of sodium hydroxide (0.1 g, 2.5 mmol) in ethanol (50 mL) and water (1 mL) and the reaction mixture was stirred overnight at room temperature. The solvent was removed under vacuum and the residue purified by silica gel column chromatography, eluting with chloroform-methanol-acetic acid, 90:9:1. Compound 14 was obtained as a reddish-brown solid (103 mg, 44.7%, after 2 steps): mp 360° C. (dec). IR (Film) 3325, 2928, 1692, 1657, 1600, 1580, 1533, 1435, 1319, 1197, 903, 701 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 10.9 (s, 1H), 8.70 (s, 1H), 8.35 (d, J=8.2 Hz, 1H), 8.02 (s, 1H), 7.90 (br s, 1H), 7.45 (m, 3H), 3.89 (s, 3H); 13C NMR (125 MHz, DMSO-d6) δ 190.1, 162.4, 162.2, 157.9, 156.3, 137.5, 136.9, 134.6, 134.0, 131.4, 128.4, 126.9, 124.4, 123.5, 123.4, 122.8, 118.5, 106.9; ESIMS m/z (rel intensity) 347 [(M-H+)−]; negative ion; HRESIMS calcd for C19H12N2O5 347.0668 [(M-H+)−]. found 347.0664 [(M-H+)−]; HPLC purity: 95.2% (MeOH—H2O, 85:15), 95.7% (MeOH—H2O, 75:25).

Workup

  1. extractionextracted with chloroform (4×50 mL)
  2. customThe solvent was removed under vacuum
  3. washeluting with chloroform-methanol, 9:1
  4. stirringthe reaction mixture was stirred overnight at room temperature
  5. customThe solvent was removed under vacuum
  6. customthe residue purified by silica gel column chromatography
  7. washeluting with chloroform-methanol-acetic acid, 90:9:1

Sources & evidence

ORD record
ord-5eeef707720243ffbeee17b19655368c
Source dataset
uspto-grants-2016_08
Patent number
US09402842B2

Reaction notes

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