Dimethylformamide → HCID 178492199, compound

HRID 511032Notes

Reaction equation

[NH:1]1[CH2:4][CH:3]([C:5]2[C:6]([O:25][CH3:26])=[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[Cl:11])[CH2:2]1.C(N(CC)CC)C.[F:34][C:35]([F:45])([F:44])S(O[CH2:40][CH:41]([F:43])[F:42])(=O)=O.CN([CH:49]=[O:50])C>>[F:34][C:35]([F:45])([F:44])[C:49]([OH:50])=[O:25].[F:34][C:35]([F:45])([F:44])[C:49]([OH:50])=[O:25].[Cl:11][C:10]1[C:9]([Cl:12])=[CH:8][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])=[C:6]([O:25][CH3:26])[C:5]=1[CH:3]1[CH2:2][N:1]([CH2:40][CH:41]([F:43])[F:42])[CH2:4]1

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 8471Triethylamine

HCID 27740892,2-Difluoroethyl trifluoromethanesulfonate

HCID 178492198HCID 178492198, compound

Product 1

HCID 178492199HCID 178492199, compoundYield 46%

Conditions

Temperature: 0 °C

Procedure

A solution of N-[1-(3-azetidin-3-yl-4,5-dichloro-2-methoxyphenyl)ethyl]-9H-purin-6-amine (15 mg, 0.038 mmol, from Example 194, Step 8) in DMF (1 mL) was treated with triethylamine (13 μL, 0.095 mmol), cooled to 0° C., treated with 2,2-difluoroethyl trifluoromethanesulfonate (12 mg, 0.058 mmol) and stirred at 0° C. for 20 minutes. The reaction mixture was purified by preparative LCMS (XBridge C18 Column, eluting with a gradient of acetonitrile in water with 0.1% trifluoroacetic acid, at flow rate of 60 mL/min) to give the desired product (12 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 8.61 (br s, 1H), 8.40-8.11 (m, 2H), 7.76 (s, 1H), 5.89-5.55 (m, 1H), 4.66-4.33 (m, 7H), 3.90-3.65 (m, 4H), 1.49 (d, J=6.1 Hz, 3H). LCMS for C19H21Cl2F2N6O (M+H)+: m/z=457.1, 459.1. Found: 457.1, 459.1.

Workup

customThe reaction mixture was purified by preparative LCMS (XBridge C18 Column
washeluting with a gradient of acetonitrile in water with 0.1% trifluoroacetic acid, at flow rate of 60 mL/min)

Sources & evidence

ORD record: ord-b86062281ba84f8a85d993aa7b5de1de
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096600B2

Reaction notes

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