Potassium Carbonate → 1-(4-{4-[7-amino-2-(4-fluoro-1,2-benzothiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone diformate salt

HRID 389514Notes

Reaction equation

HRID 389514 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9](Cl)[O:8][C:7]=12.[F:26][C:27]1[C:32]2[CH:33]=[N:34][S:35][C:31]=2[C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1.[C:45](=O)([O-:47])[O-:46].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH:45]([OH:47])=[O:46].[CH:45]([OH:47])=[O:46].[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:12]2[CH:13]=[N:14][N:15]([CH:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9]([C:30]3[C:31]4[S:35][N:34]=[CH:33][C:32]=4[C:27]([F:26])=[CH:28][CH:29]=3)[O:8][C:7]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 66759397HCID 66759397, compoundHCID 667598784-Fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-benzothiazole

Product 1

HCID 533789171-(4-{4-[7-amino-2-(4-fluoro-1,2-benzothiazol-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone diformate saltYield 19%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 1-{4-[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (15.0 mg, 0.0417 mmol), 4-fluoro-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-benzothiazole (23.3 mg, 0.0824 mmol), Pd(PPh3)4 (4.82 mg, 0.00417 mmol), potassium carbonate (17.3 mg, 0.125 mmol) and 4:1 dioxane:H2O (1 mL) was heated in a microwave reactor at 110° C. for 40 min. The crude reaction mixture was purified by preparative HPLC to afford 3.8 mg (19%) the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 1.97-2.15 (m, 2 H), 2.19 (s, 3 H), 2.19-2.30 (m, 2 H), 2.88 (td, J=13.0, 2.8 Hz, 1 H), 3.33-3.40 (m, 1 H), 4.07-4.16 (m, 1 H), 4.54 (tt, J=11.5, 4.2 Hz, 1 H), 4.65-4.74 (m, 1 H), 7.27 (dd, J=9.3, 8.3 Hz, 1 H), 7.41 (s, 1 H), 7.83 (s, 1H), 7.87 (s, 1 H), 8.09 (s, 1H), 8.20 (s, 2 H), 8.22 (dd, J=8.3, 4.5 Hz, 1 H), 9.06 (s, 1 H); MS (ESI): 477.13 [M+H]+; HPLC tR=1.10 min (TOF: polar—3 min).

Workup

  1. customThe crude reaction mixture
  2. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-288bd4dcf4cf42128d443bed41ab5b05
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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