Hydrochloric Acid → (R)-1-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)pyrrolidin-3-amine

HRID 1775015Notes

Reaction equation

[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:26][CH2:25][C@@H:24]([NH:27]C(=O)OC(C)(C)C)[CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][N:13](C4CCCCO4)[C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1.Cl>C(Cl)Cl.CO.O1CCOCC1>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]3[C:15]([C:16]4[N:21]=[C:20]([N:22]5[CH2:26][CH2:25][C@@H:24]([NH2:27])[CH2:23]5)[CH:19]=[CH:18][CH:17]=4)=[N:14][NH:13][C:10]3=[CH:11][N:12]=2)[CH:4]=[N:3]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of tert-butyl (3R)-1-(6-(5-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-3-yl)pyridin-2-yl)pyrrolidin-3-ylcarbamate (60.0 mg, 0.12 mmol) in anhydrous DCM (5.0 mL) and methanol (2.5 mL) was added 4M HCl in 1,4-Dioxane (4.0 mL). The reaction mixture was stirred at 60° C. under N2 for 18 h. Volatile solvent was evaporated in vacuo. The crude was redissolved in DMSO (1 mL) and was purified by reverse phase HPLC to give 189 as a white solid (25.5 mg, 58.4%). 1H NMR (400 MHz, DMSO) δ 9.02 (s, 1H), 8.71 (s, 1H), 8.13 (s, 1H), 7.87 (s, 1H), 7.59 (t, J=7.9 Hz, 1H), 7.36 (d, J=7.4 Hz, 1H), 6.41 (d, J=8.4 Hz, 1H), 3.91 (s, 3H), 3.81-3.64 (m, 4H), 3.63-3.52 (m, 2H), 2.17 (dt, J=12.3, 6.5 Hz, 2H), 1.88-1.75 (m, 2H). LC/MS: m/z 361.1 [M+1]

Workup

customVolatile solvent was evaporated in vacuo
dissolutionThe crude was redissolved in DMSO (1 mL)
customwas purified by reverse phase HPLC

Sources & evidence

ORD record: ord-aedc5f1bb78f4e04bf8ae93c0d8c6267
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260425B2

Reaction notes

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