Formaldehyde → HCID 178466730, compound

HRID 510955Notes

Reaction equation

HRID 510955 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:25][CH2:26][CH3:27])=[C:7]([CH:13]([NH:15][C:16]3[N:24]=[CH:23][N:22]=[C:21]4[C:17]=3[N:18]=[CH:19][NH:20]4)[CH3:14])[CH:8]=[C:9]([Cl:12])[C:10]=2[CH3:11])[CH2:2]1.[CH3:28]CN(C(C)C)C(C)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C1COCC1.C(#N)C>[Cl:12][C:9]1[C:10]([CH3:11])=[C:5]([CH:3]2[CH2:4][N:1]([CH3:28])[CH2:2]2)[C:6]([O:25][CH2:26][CH3:27])=[C:7]([CH:13]([NH:15][C:16]2[N:24]=[CH:23][N:22]=[C:21]3[C:17]=2[N:18]=[CH:19][NH:20]3)[CH3:14])[CH:8]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 178466729HCID 178466729, compound

Product 1

HCID 178466730HCID 178466730, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

Benzyl 3-{3-chloro-6-ethoxy-2-methyl-5-[1-(9H-purin-6-ylamino)ethyl]phenyl}azetidine-1-carboxylate (83 mg, 0.16 mmol) and 5% palladium (74 mg) was combined in methanol (5 mL), to which was added 0.25 M HCl in water (1.6 mL, 0.40 mmol). The suspension was hydrogenated under balloon pressure of H2 at room temperature overnight. The suspension was filtered and concentrated to give N-[1-(3-azetidin-3-yl-5-chloro-2-ethoxy-4-methylphenyl)ethyl]-9H-purin-6-amine. LCMS calculated for C19H24ClN6O (M+H)+: m/z=387.2. found: 387.1. The azetidine made above was combined with DIPEA (0.1 mL, 0.6 mmol) in methanol (0.5 mL)/acetonitrile (0.5 mL)/THF (0.5 mL), followed by the addition of 37% formaldehyde (0.1 mL, 2 mmol). The mixture was stirred at room temperature for 10 min before the addition of sodium triacetoxyborohydride (0.17 g, 0.80 mmol). The reaction mixture was stirred at room temperature overnight, then diluted with MeOH and purified on RP-HPLC (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product. LCMS calculated for C20H26ClN6O (M+H)+: m/z=401.2. found: 401.1.

Workup

  1. custompurified on RP-HPLC (XBridge C18 Column
  2. washeluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-8a9445af310042b29de6e6f9cade9a04
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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