Ammonium Hydroxide → HCID 118599092, compound

HRID 1050387Notes

Reaction equation

HRID 1050387 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][N:15]=3)[C:10](=[O:20])[N:9]3[C:21]4([CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]4)[NH:22][C:23](=[O:24])[C:8]=23)[CH2:3][CH2:2]1.[OH-].[NH4+].[H][H]>CO.O1CCCC1.[Pd].ClCCl>[N:17]1[CH:18]=[CH:19][C:14]([NH:13][C:11]2[C:10](=[O:20])[N:9]3[C:21]4([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]4)[NH:22][C:23](=[O:24])[C:8]3=[C:7]([CH:4]3[CH2:5][CH2:6][O:1][CH2:2][CH2:3]3)[CH:12]=2)=[N:15][CH:16]=1

Participants

8

Reactant 3

HCID 14923Ammonium HydroxideHCID 118598618HCID 118598618, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 118599092HCID 118599092, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A double neck round bottom flask was charged with 8′-(3,6-dihydro-2H-pyran-4-yl)-6′-(pyrimidin-4-ylamino)-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione (3, 0.22 g, 0.57 mmol) in methanol (10 mL) and tetrahydrofuran (10 mL). Palladium on carbon (0.10 g) was added followed by ammonium hydroxide (1.0 mL) under nitrogen atmosphere. The reaction was filled with hydrogen and stirred at room temperature for 3 d. After completion of reaction monitored by TLC and LCMS, the reaction mass was diluted with 5% methanol in dichloromethane (100 mL) and passed through celite bed and washed with 10% methanol/dichloromethane (3×50 mL). Solvent was removed under vacuum and crude material was purified by prep HPLC to afford 6′-(pyrimidin-4-ylamino)-8′-(tetrahydro-2H-pyran-4-yl)-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione (Cpd. No. 201) as a white solid. Yield: 0.11 g, 49%; MS (ESI) m/z 396.4 [M+1]+; 1H NMR (400 MHz, DMSO-d6) δ 10.16 (6, 1H), 9.40 (s, 1H), 8.85 (s, 1H), 8.81 (s, 1H), 8.38 (d, J=5.88 Hz, 1H), 7.37 (d, J=5.88 Hz, 1H), 4.20 (m, 1H), 3.96 (m, 2H), 3.42 (t, J=11.3 Hz, 2H), 3.01 (m, 2H), 1.70 (m, 9H), 1.58 (m, 2H), 1.22 (m, 1H).

Workup

  1. customAfter completion of reaction
  2. washwashed with 10% methanol/dichloromethane (3×50 mL)
  3. customSolvent was removed under vacuum and crude material
  4. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-a26beb38cd4d49cf91b3c9e0af9128a3
Source dataset
uspto-grants-2016_07
Patent number
US09382248B2

Reaction notes

Loading…