Methanesulfonic Acid → HCID 178461645, compound

HRID 1798915Notes

Reaction equation

HRID 1798915 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C@H:11]([CH3:15])[C:12](O)=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH2:16][NH:17][C:18]([NH:20][NH2:21])=[S:19].CS(O)(=O)=O.C(=O)(O)[O-].[Na+]>C1S(=O)(=O)CCC1.O>[SH:19][C:18]1[N:20]([NH2:21])[C:12]([C@H:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:1]=[CH:2][CH:3]=[CH:4]3)[CH3:15])=[N:16][N:17]=1

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 516892Sodium BicarbonateHCID 2724189ThiocarbohydrazideHCID 29417670HCID 29417670, compound

Product 1

HCID 178461645HCID 178461645, compoundYield 63.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 31347SulfolaneSolvent

Conditions

Temperature
90 °C

Procedure

As shown in step v of Scheme 1, (S)-2-(quinolin-6-yl)propanoic acid (50 g, 248.5 mmol) and 1,3-diaminothiourea (29.02 g, 273.4 mmol) were suspended in a mixture of tetramethylene sulfone (sulfolane, 38 mL) and water (57 mL). Methane sulfonic acid (35.5 ml, 546.7 mmol) was added to the mixture, whereupon all solids dissolved. The reaction temperature was slowly increased to 90° C. and the reaction was heated at 90° C. for 40 hours, at which time a 68% conversion of starting material to product was observed by HPLC analysis. The reaction mixture was cooled in an ice bath and water (75 mL) was added, followed by the careful addition of saturated sodium bicarbonate (500 mL) until a pH 8 was achieved. The resulting fine purple precipitate was collected by vacuum filtration, washed with water, saturated sodium bicarbonate, water, and methyl t-butyl ether, respectively. The product was dried in a vacuum oven at 55° C. for 2 days to afford 6-((S)-1-(5-mercapto-4-amino-4H-1,2,4-triazol-3-yl)ethyl)quinoline (compound 1005, 43 g): ESMS (M+1), 272.09; 1H NMR (300.0 MHz, DMSO-d6) δ 13.65 (1H, br s), 8.86 (1H, dd, J=1.8, 8.4 Hz), 8.34 (1H, d, J=7.5 Hz), 7.98 (1H, d, J=8.7 Hz), 7.84 (1H, dd, J=1.7, 13.7 Hz), 7.82 (1H, d, J=1.5 Hz), 7.70 (1H, dd, J=1.8, 8.7 Hz), 7.50 (1H, dd, J=1.8, 8.7 Hz), 5.44 (2H, s), 4.57 (1H, q, J=7.2 Hz), 1.65 (3H, d, J=7.2 Hz). The product was 92% pure by 1H NMR analysis, with the major impurities being compound 1004 and sulfolane. Chiral HPLC analysis showed 92% ee (ChiralPak® AD-H, 70% i-propanol/hexanes; retention time: 4.98 min for S-enantiomer, 12.33 min for R-enantiomer). The product was used as is in the next step without further purification.

Workup

  1. dissolutiondissolved
  2. temperaturethe reaction was heated at 90° C. for 40 hours, at which time a 68% conversion of starting material to product
  3. temperatureThe reaction mixture was cooled in an ice bath
  4. filtrationThe resulting fine purple precipitate was collected by vacuum filtration
  5. washwashed with water, saturated sodium bicarbonate, water, and methyl t-butyl ether
  6. customThe product was dried in a vacuum oven at 55° C. for 2 days

Sources & evidence

ORD record
ord-39be11e2122941efa0f17b65fd3db0d2
Source dataset
uspto-grants-2013_01
Patent number
US08343998B2

Reaction notes

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