Water → HCID 178513729, compound

HRID 1503859Notes

Reaction equation

HRID 1503859 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:37]2[CH2:42][CH2:41][N:40](C(OC(C)(C)C)=O)[CH2:39][CH2:38]2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[N:14]=[C:13]([CH2:15][C:16]2[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:23])[C:12]2[N:24]=[CH:25][N:26](COCC[Si](C)(C)C)[C:11]=2[C:10]=1[C:35]#[N:36].O.C(=O)([O-])[O-:52].[Na+].[Na+]>S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:3]=[C:4]([N:37]2[CH2:38][CH2:39][NH:40][CH2:41][CH2:42]2)[CH:5]=[CH:6][C:7]=1[NH:8][C:9]1[N:14]=[C:13]([CH2:15][C:16]2[C:17]([Cl:23])=[CH:18][CH:19]=[CH:20][C:21]=2[Cl:22])[C:12]2[N:24]=[CH:25][NH:26][C:11]=2[C:10]=1[C:35]([NH2:36])=[O:52]

Participants

5

Reactant 3

HCID 962WaterHCID 10340Sodium CarbonateHCID 86725402HCID 86725402, compound

Product 1

HCID 178513729HCID 178513729, compound

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
80 °C

Procedure

To the product of Example 42E (200 mg, 0.27 mmol) in concentrated sulfuric acid (4 mL) at 0° C. was added water (0.4 mL) and the mixture was stirred at 0° C. for 10 minutes and at 80° C. for 40 minutes. After cooling to ambient temperature, the mixture was poured into ice-water, adjusted to pH 9 by saturated aqueous sodium carbonate and extracted with dichloromethane. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC using a gradient of 10/90 to 80/20 acetonitrile/water (containing 0.1% trifluoroacetic acid) to give the title compound. 1H NMR (DMSO-d6, 300 MHz): δ 13.66 (s, 1H), 11.86 (s, 1H), 9.58 (s, 1H), 8.76 (brs, 2H), 8.63 (s, 1H), 7.83-7.78 (m, 2H), 7.61 (d, J=8.1 Hz, 2H), 7.49-7.43 (m, 2H), 7.01 (d, J=2.4 Hz, 1H), 6.43 (dd, J=9.0, 2.4 Hz, 1H), 4.73 (s, 2H), 3.27 (s, 8H). MS: 530 (M+H+).

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with dichloromethane
  3. washThe organic phase was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-533f91552bbb4168800ddd790fca733d
Source dataset
uspto-grants-2015_12
Patent number
US09212192B2

Reaction notes

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