Hydrochloric Acid → HCID 178518885, compound

HRID 634168Notes

Reaction equation

HRID 634168 reaction equation
CS([C:5]1[S:9][C:8]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[N:15](C(OC(C)(C)C)=O)[CH:14]=[C:13]3[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[N:27]=2)=[N:7][N:6]=1)(=O)=O.[OH-:38].[Na+].Cl>>[O:35]1[CH2:34][CH2:33][N:32]([C:28]2[N:27]=[C:26]([C:13]3[C:12]4[C:16](=[CH:17][CH:18]=[C:10]([C:8]5[S:9][C:5]([OH:38])=[N:6][N:7]=5)[CH:11]=4)[NH:15][CH:14]=3)[CH:31]=[CH:30][CH:29]=2)[CH2:37][CH2:36]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68328178HCID 68328178, compound

Product 1

HCID 178518885HCID 178518885, compoundYield 14.2%

Conditions

Temperature
120 °C

Procedure

A glass microwave reaction vessel was charged with tert-butyl 5-(5-(methylsulfonyl)-1,3,4-thiadiazol-2-yl)-3-(6-morpholinopyridin-2-yl)-1H-indole-1-carboxylate (160.0 mg, 0.296 mmol) and aq. 10 M NaOH (1.5 mL, 15.0 mmol). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Uppsala, Sweden) at 120° C. for 30 min. The mixture was neutralized with aq. 5 N HCl and the mixture was extracted with CHCl3/iPrOH (4:1). The combined organic layers were dried, filtered and concentrated. The crude product was dissolved in MeOH/p-dioxane (2:1, 3 mL) and catalytic amount of Pd/C was added. The mixture was stirred under H2 for 2 h, then filtered through a plug of celite. The filtrate was concentrated and the residue was purified with RP-HPLC to give 5-(3-(6-morpholinopyridin-2-yl)-1H-indol-5-yl)-1,3,4-thiadiazol-2-ol (16.0 mg, 0.042 mmol, 14%) as a pink solid. MS (ESI, pos. ion) m/z 380 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.87 (1H, br. s.), 11.71 (1H, br. s.), 8.83 (1H, s), 8.12 (1H, d, J=2.5 Hz), 7.46-7.63 (3H, m), 7.20 (1H, d, J=7.6 Hz), 6.63 (1H, d, J=8.2 Hz), 3.76-3.87 (4H, m), 3.53-3.65 (4H, m).

Workup

  1. customA glass microwave reaction vessel
  2. extractionthe mixture was extracted with CHCl3/iPrOH (4:1)
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in MeOH/p-dioxane (2:1, 3 mL)
  7. additioncatalytic amount of Pd/C was added
  8. stirringThe mixture was stirred under H2 for 2 h
  9. filtrationfiltered through a plug of celite
  10. concentrationThe filtrate was concentrated
  11. customthe residue was purified with RP-HPLC

Sources & evidence

ORD record
ord-a7681aeb923c44a190b0bfc3cf32fa17
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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