Methyl Isocyanate → Trifluoroacetic acid

HRID 510932Notes

Reaction equation

HRID 510932 reaction equation
[CH3:1][N:2]=[C:3]=[O:4].[F:5][C:6]([F:11])([F:10])[C:7]([OH:9])=[O:8].[F:12][C:13]([F:18])([F:17])[C:14]([OH:16])=[O:15].[NH:19]1[CH2:22][CH:21]([C:23]2[C:24]([O:43][CH3:44])=[C:25]([CH:31]([NH:33][C:34]3[N:42]=[CH:41][N:40]=[C:39]4[C:35]=3[N:36]=[CH:37][NH:38]4)[CH3:32])[CH:26]=[C:27]([Cl:30])[C:28]=2[CH3:29])[CH2:20]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:5][C:6]([F:11])([F:10])[C:7]([OH:9])=[O:8].[Cl:30][C:27]1[C:28]([CH3:29])=[C:23]([CH:21]2[CH2:22][N:19]([C:3]([NH:2][CH3:1])=[O:4])[CH2:20]2)[C:24]([O:43][CH3:44])=[C:25]([CH:31]([NH:33][C:34]2[N:42]=[CH:41][N:40]=[C:39]3[C:35]=2[N:36]=[CH:37][NH:38]3)[CH3:32])[CH:26]=1.[C:14]([OH:16])([C:13]([F:18])([F:17])[F:12])=[O:15]

Participants

6

Reactant 3

HCID 12228Methyl IsocyanateHCID 81531DiisopropylethylamineHCID 178492189HCID 178492189, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 178485818HCID 178485818, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methyl isocyanate (1.3 μL, 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 C20H25ClN7O2 (M+H)+: m/z=430.2. found: 430.2. 1H NMR (300 MHz, DMSO-d6) δ 8.32 (1H, br s), 8.18 (2H, m), 7.44 (1H, s), 6.31 (1H, m), 5.68 (1H, m), 4.20 (3H, m), 3.96 (1H, m), 3.82 (1H, m), 3.75 (3H, s), 2.52 (3H, s), 2.15 (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-1867bee1576541d4b2a8d814de5d19ae
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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