Tetrahydrofuran → HCID 118598799, compound

HRID 1050389Notes

Reaction equation

HRID 1050389 reaction equation
[O:1]1CCCC1.[CH3:6][C:7]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[CH:18][N:17]=[C:16]([NH:20]C(C3CC3)=O)[CH:15]=2)[C:10](=[O:26])[N:9]2[C:27]3([CH2:35][CH2:34][CH2:33][C:32](=O)[CH2:31]3)[NH:28][C:29](=[O:30])[C:8]=12.[OH-].[K+].[BH4-].[Na+]>C(O)C>[NH2:20][C:16]1[N:17]=[CH:18][N:19]=[C:14]([NH:13][C:11]2[C:10](=[O:26])[N:9]3[C:27]4([CH2:31][CH2:32][CH:33]([OH:1])[CH2:34][CH2:35]4)[NH:28][C:29](=[O:30])[C:8]3=[C:7]([CH3:6])[CH:12]=2)[CH:15]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 118598987HCID 118598987, compound

Product 1

HCID 118598799HCID 118598799, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A flask containing tetrahydrofuran and ethanol (1:1, 20 mL) was charged with N-(6-((8′-methyl-1′,3,5′-trioxo-1′,5′-dihydro-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridin]-6′-yl)amino)pyrimidin-4-yl)cyclopropanecarboxamide (5, 0.4 g, 0.9 mmol) and 3 M potassium hydroxide solution (8.0 mL) was added to the above reaction. The reaction was stirred at room temperature for 18 h. After complete hydrolysis, sodium borohydride (0.18 g, 0.4 mmol) was added to the above reaction at room temperature. The reaction mass was stirred for 2 h when TLC showed completion of starting material. The solvents were removed under reduced pressure and crude was dissolved in 10% methanol in dichloromethane and neutralized with 10% citric acid. The organic layer was separated and dried over sodium sulfate, filtered and concentrated to obtain solid. The solid was filtered and washed with methanol (5 mL) and pentane (20 mL) and dried under high vacuum to afford 6′-((6-aminopyrimidin-4-yl)amino)-4-hydroxy-8′-methyl-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione (Cpd. No. 205) as yellow solid as a mixture of diastereomers. Yield: 0.045 g, 13%; MS (ESI) m/z 357.19 [M+1]+; 1H NMR: (400 MHz, DMSO-d6) δ 9.89 & 8.48 (2 s, 1H each, isomer A & B), 8.59 & 8.57 (2 s, 1H each, isomer A & B), 8.42 (brs, 1H), 8.16 (brs, 1H), 6.52 (brs, 2H), 6.16 (brs, 1H), 5.16 & 4.85 (2 s, 1H each, isomer A & B), 4.22 and 3.73 (2 m, 1H each, isomer A & B), 2.99 & 2.88 (2 m, 2H each, isomer A & B), 2.42 (s, 3H), 1.98-1.11 (m, 6H).

Workup

  1. additionwas added to the above reaction
  2. additionwas added to the above reaction at room temperature
  3. stirringThe reaction mass was stirred for 2 h when TLC
  4. customThe solvents were removed under reduced pressure and crude
  5. dissolutionwas dissolved in 10% methanol in dichloromethane and neutralized with 10% citric acid
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto obtain solid
  11. filtrationThe solid was filtered
  12. washwashed with methanol (5 mL) and pentane (20 mL)
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-c640b9e6d2b3484e814723eacf445485
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

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