Methyl chloroformate → Trifluoroacetic acid

HRID 510931Notes

Reaction equation

HRID 510931 reaction equation
Cl[C:2]([O:4][CH3:5])=[O:3].[F:6][C:7]([F:12])([F:11])[C:8]([OH:10])=[O:9].[F:13][C:14]([F:19])([F:18])[C:15]([OH:17])=[O:16].[NH:20]1[CH2:23][CH:22]([C:24]2[C:25]([O:44][CH3:45])=[C:26]([CH:32]([NH:34][C:35]3[N:43]=[CH:42][N:41]=[C:40]4[C:36]=3[N:37]=[CH:38][NH:39]4)[CH3:33])[CH:27]=[C:28]([Cl:31])[C:29]=2[CH3:30])[CH2:21]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:6][C:7]([F:12])([F:11])[C:8]([OH:10])=[O:9].[Cl:31][C:28]1[C:29]([CH3:30])=[C:24]([CH:22]2[CH2:21][N:20]([C:2]([O:4][CH3:5])=[O:3])[CH2:23]2)[C:25]([O:44][CH3:45])=[C:26]([CH:32]([NH:34][C:35]2[N:43]=[CH:42][N:41]=[C:40]3[C:36]=2[N:37]=[CH:38][NH:39]3)[CH3:33])[CH:27]=1.[C:15]([OH:17])([C:14]([F:19])([F:18])[F:13])=[O:16]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 178492189HCID 178492189, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178501906HCID 178501906, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl chloroformate (1.6 pt, 0.021 mmol) was added to a solution of N-[1-(3-azetidin-3-yl-5-chloro-2-methoxy-4-methylphenyl)ethyl]-9H-purin-6-amine bis(trifluoroacetate) (8.5 mg, 0.014 mmol, from Example 165) and DIPEA (0.015 mL, 0.085 mmol) in methylene chloride (0.5 mL) at 0° C. and then the reaction was stirred at room temperature for 30 minutes. The crude mixture was purified on prep-LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.05% trifluoroacetic acid, at flow rate of 30 mL/min) to afford the desired product as TFA salt. LCMS calculated for C20H24ClN6O3 (M+H)+: m/z=431.2. found: 431.1. 1H NMR (300 MHz, DMSO-d6) δ 8.30 (1H, br s), 8.18 (2H, m), 7.46 (1H, s), 5.68 (1H, m), 4.31 (3H, m), 4.14 (1H, m), 4.02 (1H, m), 3.75 (3H, s), 3.55 (3H, s), 2.16 (3H, s), 1.44 (3H, d, J=6.9 Hz) ppm.

Workup

  1. customThe crude mixture was purified on prep-LCMS (XBridge C18 Column
  2. washeluting with a gradient of acetonitrile in water with 0.05% trifluoroacetic acid, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-19da944a21164796981e6651a1ba3e0a
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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