Hydrochloric Acid → 5-{7-amino-4-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[2,3-c]pyridin-2-yl}-2-chlorobenzoic acid hydrochloride

HRID 389497Notes

Reaction equation

HRID 389497 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(=O)C)[CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9]([Cl:11])[O:8][C:7]=12.[Cl:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][C:28]=1[C:36]([O:38]C)=[O:37].C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCOCC1.C(OCC)(=O)C.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>[ClH:11].[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][NH:20][CH2:19][CH2:18]3)[CH:16]=2)=[C:6]2[CH:10]=[C:9]([C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[C:28]([CH:29]=3)[C:36]([OH:38])=[O:37])[O:8][C:7]=12

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 230053344-Chloro-3-(methoxycarbonyl)benzeneboronic acidHCID 66759397HCID 66759397, compound

Product 1

HCID 667609005-{7-amino-4-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[2,3-c]pyridin-2-yl}-2-chlorobenzoic acid hydrochlorideYield 33.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 1-{4-[4-(7-amino-2-chlorofuro[2,3-c]pyridin-4-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (125 mg, 0.347 mmol), 4-chloro-3-(methoxycarbonyl)phenylboronic acid (89.4 mg, 0.417 mmol), and Pd(PPh3)4 (40.1 mg, 0.0347 mmol) in 1.0 M aqueous sodium carbonate (1.74 mL, 1.74 mmol) and 1,4-dioxane (1.63 mL) was heated to 120° C. in a microwave for 30 min. The reaction mixture was then diluted with ethyl acetate (10 mL) and acidified with aqueous 1 N hydrochloric acid (5 mL), causing formation of a precipitate. The precipitate was collected by vacuum filtration and then triturated from DMSO and methanol (10 mL, ˜1:10) to afford 55 mg (29%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.45 (d, J=1.5 Hz, 1H), 8.29 (s, 1H), 8.22 (dd, J=1.8, 8.3 Hz, 1H), 8.00 (d, J=8.1 Hz, 2H), 7.91 (s, 1H), 7.75 (d, J=8.6 Hz, 1H), 6.56 (br s, 2H), 4.61-4.30 (m, 2H), 3.94 (br s, 1H), 3.24 (br s, 1H), 2.74 (br s, 1H), 2.26-1.63 (m, 7H); MS (ESI): 480.10 [M+H]+; HPLC tR=2.35 min (ZQ3, polar—4 min).

Workup

  1. filtrationThe precipitate was collected by vacuum filtration
  2. customtriturated from DMSO and methanol (10 mL, ˜1:10)

Sources & evidence

ORD record
ord-0227b81e6c02476395f80ffec77ccae4
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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