Potassium Carbonate → HCID 66760278, compound

HRID 389589Notes

Reaction equation

IC1C=NC(N)=C2OC(C3C4C(=CN=CC=4)N(C)N=3)=CC=12.I[C:23]1[CH:28]=[N:27][C:26]([NH2:29])=[C:25]2[O:30][C:31]([C:33]3[N:34]([CH3:42])[N:35]=[C:36]4[C:41]=3[CH:40]=[CH:39][N:38]=[CH:37]4)=[CH:32][C:24]=12.CC1(C)C(C)(C)OB([C:51]2[CH:52]=[N:53][N:54]([CH:56]3[CH2:61][CH2:60][N:59]([C:62](=[O:64])[CH3:63])[CH2:58][CH2:57]3)[CH:55]=2)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[NH2:29][C:26]1[N:27]=[CH:28][C:23]([C:51]2[CH:52]=[N:53][N:54]([CH:56]3[CH2:57][CH2:58][N:59]([C:62](=[O:64])[CH3:63])[CH2:60][CH2:61]3)[CH:55]=2)=[C:24]2[CH:32]=[C:31]([C:33]3[N:34]([CH3:42])[N:35]=[C:36]4[C:41]=3[CH:40]=[CH:39][N:38]=[CH:37]4)[O:30][C:25]=12

Participants

Conditions

Temperature: 80 °C

Procedure

A 2:1 mixture of 4-iodo-2-(1-methyl-1H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-7-amine and 4-iodo-2-(2-methyl-2H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-7-amine (0.042 g, 0.102 mmol) and 1-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (0.041 g, 0.13 mmol) were dissolved in 1,4-dioxane (2 mL) and water (0.8 mL). The mixture was degassed with nitrogen for 10 min. To this mixture was added potassium carbonate (0.0530 g, 0.383 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride dichloromethane adduct (0.0104 g, 0.0128 mmol), and the mixture was heated to 80° C. for 5 h. Purification of the residue by MDP afforded 0.0143 g (29%) of 1-(4-{4-[7-amino-2-(1-methyl-1H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)pethanone as a yellow gum (Ex. 363), and 0.0075 g (30%) 1-(4-{4-[7-amino-2-(2-methyl-2H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone as a yellow gum (Ex. 364). 1-(4-{4-[7-amino-2-(1-methyl-1H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone: 1H NMR (400 MHz, CD3OD): δ 9.77 (s, 1 H), 9.11 (d, J=5.8 Hz, 1 H), 8.60 (d, J=6.3 Hz, 1 H), 8.35 (s, 1 H), 8.03 (d, J=0.5 Hz, 1 H), 7.97 (s, 1 H), 7.89 (s, 1 H), 4.76-4.67 (m, 1 H), 4.61 (tt, J=4.1, 11.4 Hz, 1 H), 4.51 (s, 3 H), 4.18-4.09 (m, 1 H), 3.44-3.35 (m, 1 H), 2.90 (dt, J=2.5, 13.0 Hz, 1 H), 2.33-2.21 (m, 2 H), 2.20 (s, 3 H), 2.18-2.10 (m, 1 H), 2.10-1.98 (m, 1 H); MS (ESI): 457.37 [M+H]+; HPLC tR=2.23 min. 1-(4-{4-[7-amino-2-(2-methyl-2H-pyrazolo[3,4-c]pyridin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone: 1H NMR (400 MHz, CD3OD): δ 9.85 (s, 1 H), 8.90 (d, J=6.6 Hz, 1 H), 8.39 (d, J=6.8 Hz, 1 H), 8.35 (s, 1 H), 8.07 (s, 1 H), 7.97 (s, 1 H), 7.91 (s, 1 H), 4.83 (s, 3 H), 4.73-4.65 (m, 1 H), 4.59 (tt, J=4.2, 11.4 Hz, 1 H), 4.16-4.07 (m, 1 H), 3.41-3.32 (m, 1 H), 2.88 (dt, J=2.5, 12.9 Hz, 1 H), 2.29-2.18 (m, 2 H), 2.17 (s, 3 H), 2.16-2.08 (m, 1 H), 2.08-1.95 (m, 1 H); MS (ESI): 457.37 [M+H]+; HPLC tR=2.14 min.

Workup

customThe mixture was degassed with nitrogen for 10 min
customPurification of the residue by MDP

Sources & evidence

ORD record: ord-445ed81f8def4adfadbcd02bb4873231
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378104B2

Reaction notes

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