Sodium Carbonate → 5-{8-[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-ylamino]-imidazo[1,2-a]pyrazin-5-yl}-2,3-dihydro-isoindol-1-one

HRID 1924989

Reaction equation

HRID 1924989 reaction equation
[N:1]1(C2C=[CH:11][C:10]([NH:13][C:14]3[C:15]4[N:16]([CH:30]=[CH:31][N:32]=4)[C:17]([C:20]4[CH:21]=[C:22]5[C:26](=[CH:27][CH:28]=4)[C:25](=[O:29])[NH:24][CH2:23]5)=[CH:18][N:19]=3)=[CH:9][CH:8]=2)CCOCC1.BrC1N2C=CN=C2C(NC2C=[N:46][C:47]([N:50]3[CH2:55][CH2:54][N:53]([CH:56]([CH3:58])[CH3:57])[CH2:52][CH2:51]3)=CC=2)=NC=1.CC1(C)C(C)(C)OB(C2C=C3C(=CC=2)C(=O)NC3)O1.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>[NH3:1].[CH:56]([N:53]1[CH2:52][CH2:51][N:50]([C:47]2[N:46]=[CH:11][C:10]([NH:13][C:14]3[C:15]4[N:16]([CH:30]=[CH:31][N:32]=4)[C:17]([C:20]4[CH:21]=[C:22]5[C:26](=[CH:27][CH:28]=4)[C:25](=[O:29])[NH:24][CH2:23]5)=[CH:18][N:19]=3)=[CH:9][CH:8]=2)[CH2:55][CH2:54]1)([CH3:58])[CH3:57]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 219557955-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoindolin-1-oneHCID 573939935-[8-(4-Morpholin-4-yl-phenylamino)-imidazo[1,2-a]pyrazin-5-yl]-2,3-dihydro-isoindol-1-oneHCID 59023102(5-Bromo-imidazo[1,2-a]pyrazin-8-yl)-[6-(4-isopropyl-piperazin-1-yl)-pyridin-3-yl]-amine

Product 2

HCID 222AmmoniaHCID 590230745-{8-[6-(4-Isopropyl-piperazin-1-yl)-pyridin-3-ylamino]-imidazo[1,2-a]pyrazin-5-yl}-2,3-dihydro-isoindol-1-oneYield 50%

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)-[6-(4-isopropyl-piperazin-1-yl)-pyridin-3-yl]-amine (0.05 g, 0.12 mmol), 5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-2,3-dihydro-isoindol-1-one (0.056 g, 0.22 mmol), 1.5M Na2CO3 (0.64 mL, 0.96 mmol) and Pd(PPh3)4 (0.042 g, 0.36 mmol) in dioxane (2 mL). Purification using silica gel column chromatography, eluting with DCM followed by 99:1 and 97:3 DCM:NH3 (7M in MeOH), affords the title compound as a yellow solid (28 mg, 50%). Conversion into the mesylate salt, as described for Compound 178, step 4, affords the title compound as a yellow solid (32 mg, 95%). LCMS: Rt 2.70 min (92%); m/z (APCI) 469 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 1.34 (6H, d), 2.34 (3H, s, MsOH), 3.10-3.21 (4H, m), 3.57-3.59 (3H, m), 4.43 (2H, d), 4.52 (2H, s), 7.08 (1H, d), 7.52 (1H, s), 7.77-7.94 (4H, m), 8.07 (1H, s), 8.30 (1H, d), 8.75 (1H, s), 8.83 (1H, br s), 9.34 (1H, br s), 9.88 (1H, br s).

Workup

  1. customPurification
  2. washeluting with DCM

Sources & evidence

ORD record
ord-e79c603c8d734e53bbbccec2ba4b04a1
Source dataset
uspto-grants-2012_05
Patent number
US08178530B2

Linked notes

Loading…