Sodium Chloride → 5-[4-(benzyloxy)phenyl]-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 51611Notes

Reaction equation

HRID 51611 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:22](Cl)=[N:21][CH:20]=[N:19][C:18]=3[N:17]([CH:25]3[CH2:34][CH2:33][C:28]4([O:32][CH2:31][CH2:30][O:29]4)[CH2:27][CH2:26]3)[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[NH4+:36].C(OCC)(=O)C.[Cl-].[Na+]>O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:22]([NH2:36])=[N:21][CH:20]=[N:19][C:18]=3[N:17]([CH:25]3[CH2:34][CH2:33][C:28]4([O:32][CH2:31][CH2:30][O:29]4)[CH2:27][CH2:26]3)[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5234Sodium ChlorideHCID 8857Ethyl AcetateHCID 14923Ammonium HydroxideHCID 227363545-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 227362125-[4-(benzyloxy)phenyl]-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 81%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-[4-(benzyloxy)phenyl]-4-chloro-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidine (1.925 g, 4.01 mmol) and concentrated ammonium hydroxide (50 ml) in dioxane (50 mL) was heated at 120° C. in a pressure vessel for 20 hours. The reaction mixture was allowed to cool to room temperature. Ethyl acetate (300 mL) and saturated sodium chloride aqueous solution (300 mL) were added. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (700 mL). The organic layers were combined, washed with water, dried over magnesium sulfate, and the solvent removed under reduced pressure. The compound was purified by flash chromatography on silica using 5% methanol in dichloromethane to give 1.457 g (81%) of 5-[4-(benzyloxy)phenyl]-7-(1,4-dioxaspiro[4.5]dec-8-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine. 1H NMR (DMSO-d6, 400 MHz) δ 8.13(s, 1H), 7.49-7.31(m, 8H), 7.121-7.100(d, 2H, J=8 Hz), 6.02(br s, 2H), 5.149(s, 2H), 4.681-4.620 (m, 1H), 3.94-3.88(m, 4H), 2.12-2.03(m, 2H), 1.93-1.90(m, 2H), 1.82-1.71(m, 4H); Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 6.924 min.

Workup

  1. temperatureto cool to room temperature
  2. customThe layers were partitioned
  3. extractionthe aqueous layer was extracted with ethyl acetate (700 mL)
  4. washwashed with water
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent removed under reduced pressure
  7. customThe compound was purified by flash chromatography on silica using 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-fec84068ec0947b993aca5d5fe56e21c
Source dataset
uspto-grants-2004_03
Patent number
US06713474B2

Reaction notes

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