Acetonitrile → 3,5-Dichloro-4-[4-(6-fluoromethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile

HRID 626691Notes

Reaction equation

HRID 626691 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:18][C:19]3[CH:24]=[C:23]([CH2:25][OH:26])[N:22]=[CH:21][N:20]=3)=[N:15][CH:16]=[CH:17][C:12]2=[N:11]1)[C:5]#[N:6].CCN(S(F)(F)[F:35])CC.C(#N)C>C(Cl)Cl.O>[OH-:26].[NH4+:6].[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:28])[C:9]=1[N:10]1[CH:27]=[C:13]2[C:14]([NH:18][C:19]3[CH:24]=[C:23]([CH2:25][F:35])[N:22]=[CH:21][N:20]=3)=[N:15][CH:16]=[CH:17][C:12]2=[N:11]1)[C:5]#[N:6]

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 123472(Diethylamino)sulfur trifluorideHCID 696713413,5-Dichloro-4-[4-(6-hydroxymethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile

Product 2

HCID 14923Ammonium HydroxideYield 0.1%HCID 677022303,5-Dichloro-4-[4-(6-fluoromethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrileYield 28.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 3,5-dichloro-4-[4-(6-hydroxymethyl-pyrimidin-4-ylamino)-pyrazolo[4,3-c]pyridin-2-yl]-benzonitrile (70 mg, 0.17 mmol) in DCM (5 mL) at −25° C. was added DAST (34 μL, 0.25 mmol). The reaction mixture was warmed to room temperature over 1 hour. The reaction mixture was partitioned between DCM and sodium bicarbonate (sat. aq.). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate in cyclohexane) then by HPLC (5 to 98% acetonitrile in water with 0.1% ammonium hydroxide) to afford the title compound as a white solid (10 mg, 14% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1H), 9.23 (s, 1H), 8.81 (s, 1H), 8.69 (s, 1H), 8.49 (s, 2H), 8.02 (d, J=6.4 Hz, 1H), 7.27 (d, J=6.4 Hz, 1H), 5.50 (d, J=46.3 Hz, 2H). LCMS (Method B): RT=2.96 min, m/z: 414 [M+H+].

Workup

  1. customThe reaction mixture was partitioned between DCM and sodium bicarbonate (sat. aq.)
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-dae28d60c03447f8ac8701b0937e4a15
Source dataset
uspto-grants-2016_04
Patent number
US09309240B2

Reaction notes

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