Ethanol → N-[1-(3-Bromo-5-fluoro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 510911Notes

Reaction equation

FC(F)(F)C(O)=O.[Br:8][C:9]1[C:10]([O:20][CH3:21])=[C:11]([CH:17]([NH2:19])[CH3:18])[CH:12]=[C:13]([F:16])[C:14]=1[CH3:15].Br[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2[CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][O:33]1.C(N(CC)C(C)C)(C)C.C(O)C>CO>[Br:8][C:9]1[C:10]([O:20][CH3:21])=[C:11]([CH:17]([NH:19][C:23]2[N:31]=[CH:30][N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][N:27]3[CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)[CH3:18])[CH:12]=[C:13]([F:16])[C:14]=1[CH3:15]

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of 1-(3-bromo-5-fluoro-2-methoxy-4-methylphenyl)ethanamine trifluoroacetate (130 mg, 0.35 mmol), 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (150 mg, 0.53 mmol, from Example 108, Step 1), N,N-diisopropylethylamine (0.31 mL, 1.8 mmol) and ethanol (2.0 mL) was heated at 95° C. for 1 hour. The resulting mixture was diluted with methanol and purified by preparative LCMS (pH 10) RP-HPLC (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min) to afford N-[1-(3-Bromo-5-fluoro-2-methoxy-4-methylphenyl)ethyl]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (40 mg, 47%). LCMS calculated for C20H24BrFN5O2 (M+H)+: m/z=464.0, 466.0. Found: 464.1, 466.1.

Workup

custompurified by preparative LCMS (pH 10)
wash(XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record: ord-36d8a620836a4122b4764b6746e1101c
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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