Sodium hydride → HCID 49818909, compound

HRID 1692891Notes

Reaction equation

HRID 1692891 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2.[H-].[Na+].Cl[C:16]1[N:24]=[C:23]2[C:19]([N:20]=[C:21]([CH2:26][N:27]3[CH2:32][CH2:31][CH:30]([C:33]([OH:36])([CH3:35])[CH3:34])[CH2:29][CH2:28]3)[N:22]2[CH3:25])=[C:18]([N:37]2[CH2:42][CH2:41][O:40][CH2:39][CH2:38]2)[N:17]=1>CN(C=O)C.O>[CH3:1][O:2][CH2:3][C:4]1[N:5]([C:16]2[N:24]=[C:23]3[C:19]([N:20]=[C:21]([CH2:26][N:27]4[CH2:32][CH2:31][CH:30]([C:33]([OH:36])([CH3:35])[CH3:34])[CH2:29][CH2:28]4)[N:22]3[CH3:25])=[C:18]([N:37]3[CH2:38][CH2:39][O:40][CH2:41][CH2:42]3)[N:17]=2)[C:6]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[CH:8][CH:7]=2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 12554057HCID 12554057, compoundHCID 596034262-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

Product 1

HCID 49818909HCID 49818909, compoundYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 2-(methoxymethyl)-1H-indole (57 mg, 0.35 mmol) in DMF (2 mL) was added sodium hydride (60% dispersion, 15 mg, 0.38 mmol) at 0° C. The mixture was stirred at 0° C. for 10 minutes before the addition of 2-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (120 mg, 0.29 mmol). The mixture was then heated in the microwave at 180° C. for 15 minutes. The reaction mixture was then diluted with water. The mixture was extracted with three times with EtOAc. The combined extracts were washed with water, dried over Na2SO4, filtered and concentrated. The crude product was then purified by flash chromatography (0-100% gradient EtOAc-heptane) followed by RP-HPLC to give 127 (29.2 mg, 19%). LCMS: M+H+=534.3. 1H-NMR (400 MHz, DMSO-d6): δ 8.18 (d, 1H), 7.57 (d, 1H), 7.20 (t, 1H), 7.12 (t, 1H), 6.66 (s, 1H), 4.98 (s, 2H), 4.25 (s, br, 4H), 4.02 (s, 1H), 3.81 (s, 3H), 3.77 (m, 4H), 3.72 (s, 2H), 2.90 (d, 2H), 1.99 (m, 2H), 1.67 (m, 2H), 1.21 (m, 3H), 1.02 (s, 6H)

Workup

  1. extractionThe mixture was extracted with three times with EtOAc
  2. washThe combined extracts were washed with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was then purified by flash chromatography (0-100% gradient EtOAc-heptane)

Sources & evidence

ORD record
ord-6dbe605becc54490a125b328554bb237
Source dataset
uspto-grants-2012_04
Patent number
US08158625B2

Reaction notes

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