Acetic Acid → HCID 58054392, compound

HRID 1874711Notes

Reaction equation

HRID 1874711 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1.C(N(CC)CC)C.C(O)(=O)C.[O-:43][C:44]#[N:45].[K+]>CCOC(C)=O.O>[NH2:45][C:44]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][N:11]2[C:19]3[C:14](=[C:15]([O:20][CH3:21])[CH:16]=[CH:17][CH:18]=3)[C:13]([NH:22][S:23]([C:26]3[S:27][C:28]([Cl:31])=[CH:29][CH:30]=3)(=[O:25])=[O:24])=[N:12]2)[CH:7]=[CH:8][CH:9]=1)=[O:43]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 11378442Potassium cyanateHCID 66632476N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride

Product 1

HCID 58054392HCID 58054392, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride ((for a preparation see Intermediate 4) 47 mg, 0.094 mmol) in ethyl acetate (0.4 mL) and triethylamine (0.013 mL, 0.094 mmol) was added acetic acid (1.5 mL). A solution of potassium cyanate (11 mg, 0.14 mmol) in water (0.2 mL) was added portionwise. The resultant clear solution was stirred at room temperature overnight. LCMS showed incomplete reaction and a higher percentage of product to SM. The reaction mixture was concentrated in vacuo and the resultant oil was divided into 2 equal portions. Each was dissolved in 1:1 MeOH:DMSO (1 mL) and purified by MDAP on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier. The appropriate fractions were combined and concentrated in vacuo to give two respective batches, which were not clean, so these were combined and re-purified by MDAP to give the title compound (2.4 mg, 5%). LCMS (System A) RT=0.95 min, ES+ve m/z 506/508 (M+H)+.

Workup

  1. customreaction
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionEach was dissolved in 1:1 MeOH
  4. customDMSO (1 mL) and purified by MDAP on Xbridge column
  5. concentrationconcentrated in vacuo
  6. customto give two respective batches, which
  7. customre-purified by MDAP

Sources & evidence

ORD record
ord-f4b7d826cebc4a8589148e0468a95d8a
Source dataset
uspto-grants-2012_11
Patent number
US08304446B2

Reaction notes

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