Tetrahydrofuran → HCID 118599033, compound

HRID 1050359Notes

Reaction equation

HRID 1050359 reaction equation
O1CCCC1.Cl[C:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[CH:18][N:17]=[C:16](NC(C3CC3)=O)[CH:15]=2)[C:10](=[O:26])[N:9]2[C:27]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34](F)C=3)(C)[NH:28][C:29](=O)[C:8]=12.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:40]>CO.ClCCl>[N:17]1[CH:16]=[CH:15][C:14]([NH:13][C:11]2[C:10](=[O:26])[N:9]3[C:27]4([CH2:32][CH2:37][CH2:36][CH2:35][CH2:34]4)[NH:28][C:29](=[S:40])[C:8]3=[CH:7][CH:12]=2)=[N:19][CH:18]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 14817Phosphorus sulfide (P2S5)HCID 118598561HCID 118598561, compound

Product 1

HCID 118599033HCID 118599033, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A vial containing tetrahydrofuran (10 mL) was charged with 6-(pyrimidin-4-ylamino)spiro[2H-imidazo[1,5-a]pyridine-3,1′-cyclohexane]-1,5-dione (1, 0.6 g, 1.93 mmol) and phosphorus pentasulfide (857 mg, 3.85 mmol). Seal the vial and heat the reaction mixture at 50° C. for 16 h. After completion, the reaction mass was diluted with 5% methanol in dichloromethane (100 mL), washed with water (2×100 mL) and brine solution (100 mL), dried over anhydrous sodium sulfate, concentrated under vacuum. Crude material was purified by flash chromatography in silica gel in 3-4% methanol in dichloromethane, fraction were combined concentrated under reduced pressure. The product was triturated with methanol, filtered washed with methanol (3 mL), ether (5 mL), dried under high vacuum to obtain the desired product 6′-(pyrimidin-4-ylamino)-1′-thioxo-1′,2′-dihydro-5′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridin]-5′-one (Cpd. No. 131) as light yellow solid. Yield: 0.050 g, 8%; MS (ESI) m/z 328.41 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 9.46 (s, 1H), 8.80-8.77 (d, 2H), 8.39-8.38 (d, 1H), 7.39-7.38 (d, 1H), 7.07-7.06 (d, 1H), 2.97 (t, 2H), 1.78-1.72 (m, 5H), 1.59-1.56 (d, 1H), 1.26 (m, 1H).

Workup

  1. customSeal the vial and
  2. washwashed with water (2×100 mL) and brine solution (100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customCrude material was purified by flash chromatography in silica gel in 3-4% methanol in dichloromethane
  6. concentrationfraction were combined concentrated under reduced pressure
  7. customThe product was triturated with methanol
  8. filtrationfiltered
  9. washwashed with methanol (3 mL), ether (5 mL)
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-7296e6f8042e40ba8efa7db343cde4ca
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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