Dimethyl Sulfoxide → 2-Fluoro-4-({-4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzamide formic acid salt

HRID 887000Notes

Reaction equation

[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([F:11])[CH:3]=1.Cl[C:13]1[N:18]=[C:17]([NH:19][CH2:20][C:21]2[C:22]([N:27]([CH3:32])[S:28]([CH3:31])(=[O:30])=[O:29])=[N:23][CH:24]=[CH:25][CH:26]=2)[C:16]([C:33]([F:36])([F:35])[F:34])=[CH:15][N:14]=1.FC(F)(F)[C:39]([OH:41])=[O:40].CS(C)=O>CC(O)C>[CH:39]([OH:41])=[O:40].[F:11][C:4]1[CH:3]=[C:2]([NH:1][C:13]2[N:18]=[C:17]([NH:19][CH2:20][C:21]3[C:22]([N:27]([CH3:32])[S:28]([CH3:31])(=[O:30])=[O:29])=[N:23][CH:24]=[CH:25][CH:26]=3)[C:16]([C:33]([F:34])([F:36])[F:35])=[CH:15][N:14]=2)[CH:10]=[CH:9][C:5]=1[C:6]([NH2:8])=[O:7]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-amino-2-fluorobenzamide (1.5 eq., 189 μM) in 2-propanol (1.0 mL) was treated with C9 (1 equiv., 130 uM) followed by trifluoroacetic acid (2.7 equiv., 341 μM) and stirred in a sealed vial at 100° C. for about 20 hours. The mixture was then cooled to 25° C., treated with DMSO, filtered, and purified on a Shimadzu using a reverse phase Symmetry C-8 column and eluting with 20-80% B for 10min at 40 ml/min (A:0.1% formic acid in water, B: 0.1% formic acid in acetonitrile to provide the formic acid salt of 13 as a cream colored solid. Yield: 17.5 mg, 27%. LC-MS M+1=514. NMR (d6-DMSO) δ: 3.13 (6H, s), 4.81 (2H, s), 7.30-7.40 (6H, m), 7.41-7.73 (2H, m), 8.3 (1H, s), 8.41 (1H, s), 9.96 (1H, s). FAK IC50: <0.000595 μM (Table 1, Example 320)

Workup

temperatureThe mixture was then cooled to 25° C.
filtrationfiltered
custompurified on a Shimadzu
washeluting with 20-80% B for 10min at 40 ml/min (A:0.1% formic acid in water, B

Sources & evidence

ORD record: ord-67a67d7f4e094d848cf548befa302c33
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247411B2

Reaction notes

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