HCID 3666186, compound → HCID 85471029, compound

HRID 1465680Notes

Reaction equation

HRID 1465680 reaction equation
[CH:1]1([N:7]2[CH2:12][CH2:11][N:10]([C:13]3[C:26]4=[N:27][O:28][C:24]5=[C:25]4[C:16]([C:17](=[O:29])[C:18]4[C:23]5=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:15]([NH:30][C:31]4[CH:39]=[CH:38][C:34]([C:35]([OH:37])=[O:36])=[CH:33][CH:32]=4)[CH:14]=3)[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+:41].CO>>[CH:1]1([N:7]2[CH2:8][CH2:9][N:10]([C:13]3[C:26]4=[N:27][O:28][C:24]5=[C:25]4[C:16]([C:17](=[O:29])[C:18]4[C:23]5=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:15]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([C:35]([O-:37])=[O:36])=[CH:38][CH:39]=4)[CH:14]=3)[CH2:11][CH2:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1.[Na+:41]

Participants

3

Reactant 2

HCID 3666186HCID 3666186, compoundHCID 23721981Sodium hydroxide methanol

Product 1

HCID 85471029HCID 85471029, compoundYield 90%

Procedure

About 80 g of 4-((3-(4-cyclohexylpiperazin-1-yl)-6-oxo-6H-anthra[1,9-cd]isoxazol-5-yl)amino)benzoic acid was slurred in 2500 mL of 0.4 M NaOH/MeOH between 40-45° C. for 2-4 hours. After confirmed the reaction completion by HPLC, slowly cooled the reaction to room temperature. The solid was centrifuged and washed with 20 mL of MTBE. The wet cake was re-suspended in about 1000 mL of 0.1M NaOH in MeOH solution under room temperature. It was centrifuged and washed with 224 mL of MTBE again. The filtered solid was suspended in 996 mL of MTBE under room temperature for 1-2 hours. The solid was separated and dried at 25-30° C. under pressure for 12-24 hours to obtain the final desired product with purity more than 99% and about 90% yield. Mass spectra give [M+1]=523.2. 1H-NMR (400 MHz, DMSO-d6, see FIG. 3), ppm (δ): 11.79 (1H, s), 8.48 (1H, d), 8.20 (1H, d), 7.93 (2H, d), 7.84 (1H, t), 7.72 (1H, t), 7.35 (2H, d), 6.39 (1H, s), 3.85 (4H, m), 2.72-2.70 (4H, m), 2.28-2.265 (1H, m), 1.72-1.78 (4H, m), 1.55-1.58 (1H, m), 1.08-1.23 (5H, m). Sodium content is 3.8%. The Raman spectrum is shown in FIG. 5. The XRPD, see Table below and FIG. 4, confirmed the polymorphic form.

Workup

  1. temperatureslowly cooled
  2. customthe reaction to room temperature
  3. washwashed with 20 mL of MTBE
  4. customwas re-suspended in about 1000 mL of 0.1M NaOH in MeOH solution under room temperature
  5. washwashed with 224 mL of MTBE again
  6. customThe solid was separated
  7. customdried at 25-30° C. under pressure for 12-24 hours

Sources & evidence

ORD record
ord-10e89f4ef9a64d44806fe28b55624862
Source dataset
uspto-grants-2015_04
Patent number
US08999992B2

Reaction notes

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