Sodium Carbonate → 2-Fluoro-4-{8-[4-(1-methyl-piperidin-4-ylmethoxy)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamide

HRID 1924932Notes

Reaction equation

HRID 1924932 reaction equation
Br[C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]3)=[CH:14][CH:13]=2)=[N:4][CH:3]=1.[F:27][C:28]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[CH:33][C:29]=1[C:30]([NH2:32])=[O:31].C([O-])([O-])=O.[Na+].[Na+]>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>[F:27][C:28]1[CH:36]=[C:35]([C:2]2[N:7]3[CH:8]=[CH:9][N:10]=[C:6]3[C:5]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH:20]4[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]4)=[CH:14][CH:13]=3)=[N:4][CH:3]=2)[CH:34]=[CH:33][C:29]=1[C:30]([NH2:32])=[O:31]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 590230642-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 59023106(5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-[4-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-amine

Product 1

HCID 582288032-Fluoro-4-{8-[4-(1-methyl-piperidin-4-ylmethoxy)-phenylamino]-imidazo[1,2-a]pyrazin-5-yl}-benzamideYield 85.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

In the same way as described for Compound 178, step 4, using (5-bromo-imidazo[1,2-a]pyrazin-8-yl)-[4-(1-methyl-piperidin-4-ylmethoxy)-phenyl]-amine (20 mg, 0.048 mmol), 2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (25.5 mg, 0.10 mmol), Pd(PPh3)4 (13.9 mg, 0.001 mmol) and 1M Na2CO3 (0.8 mL) in dioxane (2 mL). Purification by silica gel column chromatography eluting with a mixture 95:5 followed by 90:10 DCM:MeOH affords a solid that was triturated with ethyl acetate to give the title compound (19.4 mg, 85%). LCMS: Rt 1.96 min (94%), m/z (APCI) 475 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.48-1.61 (2H, m), 1.98-2.02 (3H, m), 2.51-2.58 (4H, m), 2.70 (3H, br s), 3.91 (2H, d), 6.98 (2H, d), 7.55 (1H, s), 7.65-7.87 (6H, m), 7.98 (2H, d), 8.06 (1H, s), 9.68 (1H, s).

Workup

  1. customPurification by silica gel column chromatography
  2. washeluting with a mixture 95:5
  3. customMeOH affords a solid
  4. customthat was triturated with ethyl acetate

Sources & evidence

ORD record
ord-3ec0997b1e7242ecb99210619b7777a8
Source dataset
uspto-grants-2012_05
Patent number
US08178530B2

Reaction notes

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