Potassium Carbonate → 1-(4-{4-[7-amino-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone Diformate Salt

HRID 389559Notes

Reaction equation

HRID 389559 reaction equation
I[C:2]1[CH:7]=[N:6][C:5]([NH2:8])=[C:4]2[O:9][C:10]([C:12]3[C:13]4[S:20][N:19]=[CH:18][C:14]=4[CH:15]=[N:16][CH:17]=3)=[CH:11][C:3]=12.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][N:32]([CH:34]3[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]3)[CH:33]=2)O1.[C:44](=O)([O-:46])[O-:45].[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:44]([OH:46])=[O:45].[CH:44]([OH:46])=[O:45].[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:29]2[CH:30]=[N:31][N:32]([CH:34]3[CH2:35][CH2:36][N:37]([C:40](=[O:42])[CH3:41])[CH2:38][CH2:39]3)[CH:33]=2)=[C:3]2[CH:11]=[C:10]([C:12]3[C:13]4[S:20][N:19]=[CH:18][C:14]=4[CH:15]=[N:16][CH:17]=3)[O:9][C:4]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593927031-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethanoneHCID 667603344-Iodo-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-7-amine

Product 1

HCID 533791521-(4-{4-[7-amino-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone Diformate SaltYield 38%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 4-iodo-2-([1,2]thiazolo[4,5-c]pyridin-7-yl)furo[2,3-c]pyridin-7-amine (7.0 mg, 0.018 mmol), 1-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (8.5 mg, 0.027 mmol), Pd(PPh3)4 (1.0 mg, 0.00089 mmol), potassium carbonate (7.4 mg, 0.053 mmol) and 4:1 dioxane:water (1 mL) was heated in a microwave reactor at 85° C. for 20 min. The solution was used directly for HPLC purification, and the fractions containing the pure product were concentrated in vacuo to afford 3.1 mg (38%) of the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 2.03-2.16 (m, 2 H), 2.19 (s, 3 H), 2.20-2.31 (m, 2 H), 2.88 (td, J=12.9, 2.7 Hz, 1 H), 3.34-3.41 (m, 1 H), 4.08-4.17 (m, 1 H), 4.55 (tdd, J=11.4, 11.4, 4.2, 4.0 Hz, 1 H), 4.67-4.75 (m, 1 H), 7.72 (s, 1 H), 7.89 (s, 1 H), 7.92 (s, 1 H), 8.15 (s, 1 H), 8.16 (s, 2 H), 9.23 (s, 1 H), 9.28 (s, 1 H), 9.44 (s, 1 H); MS (ESI): 460.63 [M+H]+; HPLC tR=0.56 min (TOF: polar—3 min).

Workup

  1. customThe solution was used directly for HPLC purification
  2. additionthe fractions containing the pure product
  3. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-046972a427934d02b2c44db5b183a0e6
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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