3-Cyanobenzoic acid → 4-cyano-N-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 624834Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[C:6]([NH:8][CH:9]2[CH2:11][CH2:10]2)[N:5]2[N:12]=[CH:13][C:14]([CH:15]=[O:16])=[C:4]2[N:3]=1.[CH3:17][N:18](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C([C:43]1[CH:44]=[C:45]([CH:49]=[CH:50][CH:51]=1)[C:46]([OH:48])=O)#N.CCN(C(C)C)C(C)C>C(#N)C>[C:17]([C:51]1[CH:43]=[CH:44][C:45]([C:46]([NH:1][C:2]2[CH:7]=[C:6]([NH:8][CH:9]3[CH2:11][CH2:10]3)[N:5]3[N:12]=[CH:13][C:14]([CH:15]=[O:16])=[C:4]3[N:3]=2)=[O:48])=[CH:49][CH:50]=1)#[N:18]

Participants

Conditions

Temperature: 80 °C

Procedure

To 5-amino-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (step b) (30 mg, 0.138 mmol) in 1.0 mL acetonitrile was added HATU (104 mg, 0.273 mmol), 3-cyano benzoic acid (30 mg, 0.203 mmol) and DIPEA (48.0 ul). The reaction mixture was heated to 80° C. for five hours. Cooled the reaction mixture and light yellow precipitate was filtered, washed with acetonitrile to yield 4-cyano-N-(7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide. The crude product was further dissolved in 1.0 mL ethanol, added hydantoin (10 mg, 0.01 mmol) and pipperdine (9.5 ul). The reaction was heated to 80° C. for three hours. Cooled the reaction mixture and precipitate was filtered, washed with ethanol to yield 7 mg (40% yield, two steps) (Z)-4-cyano-N-(7-(cyclopropylamino)-3-((2,5-dioxoimidazolidin-4-ylidene)methyl)pyrazolo[1,5-a]pyrimidin-5-yl)benzamide. LCMS (M+1=429)

Workup

temperatureCooled the reaction mixture and light yellow precipitate
filtrationwas filtered
washwashed with acetonitrile

Sources & evidence

ORD record: ord-198f1ce7eac64135a3d720f5da466bbb
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09303033B2

Reaction notes

Loading…