Sulfuric Acid → 4-(4-(allylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)-2-(allyloxy)benzonitrile

HRID 474289Notes

Reaction equation

[CH2:1]([O:4][C:5]1[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][C:6]=1[C:7]#[N:8])[CH:2]=[CH2:3].[CH2:14]([NH:17][C:18]1[C:19]2[CH2:27][CH2:26][C:25]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)(C)[C:20]=2[N:21]=[C:22](Cl)[N:23]=1)[CH:15]=[CH2:16].OS(O)(=O)=O>CN1CCCC1=O>[CH2:14]([NH:17][C:18]1[C:19]2[CH2:27][CH2:26][CH:25]([C:29]3[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=3)[C:20]=2[N:21]=[C:22]([NH:13][C:11]2[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[C:5]([O:4][CH2:1][CH:2]=[CH2:3])[CH:12]=2)[N:23]=1)[CH:15]=[CH2:16]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-(allyloxy)-4-aminobenzonitrile (Preparation D, 168 mg, 0.963 mmol), and N-allyl-2-chloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Ua, 204 mg, 0.642 mmol) in N-Methyl-2-pyrrolidinone (5135 μL) was added H2SO4 (54.7 μL, 1.027 mmol). The mixture was stirred at 100° C. overnight. The crude reaction mixture was purified by PREP HPLC: (50×250 mm HPLC XTerra C18.15 to 100% A:B over 40 min, 3 min at 100% B (A is 90:10:0.1 water:MeOH:TFA; B is 90:10:0.1 MeOH:water:TFA)). The appropriate fractions were concentrated in vacuo to afford 4-(4-(allylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)-2-(allyloxy)benzonitrile (74 mg, 25% yield). LC-MS (M+H)+=456.1.

Workup

customThe crude reaction mixture
customwas purified by PREP HPLC
waitto 100% A:B over 40 min
custom3 min
concentrationThe appropriate fractions were concentrated in vacuo

Sources & evidence

ORD record: ord-a6cc313fdbba40e781e5523e412ad0e6
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637523B2

Reaction notes

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