1,2-Dichloroethane → 4-(8-((4-tert-butylpiperazin-1-yl)methyl)-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine

HRID 1945943Notes

Reaction equation

HRID 1945943 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:17]=O)[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=1.ClCCCl.[C:29]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)([CH3:32])([CH3:31])[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>>[C:29]([N:33]1[CH2:38][CH2:37][N:36]([CH2:17][C:7]2[N:8]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[C:9]3[C:5]([N:6]=2)=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[N:3]=[C:2]([Cl:1])[N:10]=3)[CH2:35][CH2:34]1)([CH3:32])([CH3:31])[CH3:30]

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 35305721-Tert-butylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 596034642-chloro-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purine-8-carbaldehyde

Product 1

HCID 596055524-(8-((4-tert-butylpiperazin-1-yl)methyl)-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholineYield 62.8%

Procedure

2-Chloro-6-morpholino-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-8-carbaldehyde (0.148 g, 0.422 mmol) was dissolved in 1,2-dichloroethane (3.7 mL, 0.047 mol). 1-tert-butylpiperazine (0.060 g, 0.42 mmol) was added followed by micronized 4 Å molecular sieves (0.450 g). After 2 hours sodium triacetoxyborohydride (0.179 g, 0.844 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mixture was filtered. The filter cake was washed with additional DCM and MeOH. The combined organics were concentrated to dryness. The crude was purified by flash column chromatography (Si—PPC; MeOH:DCM gradient 0:100 to 10:90) to give 4-(8-((4-tert-butylpiperazin-1-yl)methyl)-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine (126 mg, 62%). [M+H]+=478.3

Workup

  1. filtrationThe reaction mixture was filtered
  2. washThe filter cake was washed with additional DCM and MeOH
  3. concentrationThe combined organics were concentrated to dryness
  4. customThe crude was purified by flash column chromatography (Si—PPC; MeOH:DCM gradient 0:100 to 10:90)

Sources & evidence

ORD record
ord-c642cf4a865945858f80e08e94f965d5
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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