Hydrochloric Acid → 2-Chloro-8-[2-(4,4-difluoropiperidin-1-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purine

HRID 1945650Notes

Reaction equation

HRID 1945650 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH:13]=O)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.[F:21][C:22]1([F:28])[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.Cl.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:25]3[CH2:26][CH2:27][C:22]([F:28])([F:21])[CH2:23][CH2:24]3)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27583524,4-DifluoropiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 59605819(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde

Product 1

HCID 596055962-Chloro-8-[2-(4,4-difluoropiperidin-1-yl)ethyl]-9-methyl-6-morpholin-4-yl-9H-purineYield 37%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde (60 mg, 0.20 mmol) in DCE (10 mL) was added 4,4-difluoropiperidine.HCl (42 mg, 0.26 mmol), triethylamine (0.04 mL, 0.26 mmol), powdered 4 Å molecular sieves and sodium triacetoxyborohydride (86 mg, 0.41 mmol). The reaction mixture was stirred at room temperature for 5 h, the reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by column chromatography (Si—PCC, 0-5% MeOH in DCM) to give the title compound as a pale yellow oil (30 mg, 37%). LCMS (Method H): RT=2.61 min, [M+H]+ 401.5

Workup

  1. washwashed with MeOH
  2. washthe desired product eluted with 2 M NH3/MeOH in DCM
  3. customThe resulting residue was purified by column chromatography (Si—PCC, 0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-2943386dcc4f4d2aa1d2ce352c62ee73
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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