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 1921839

反応式

HRID 1921839 の反応式
[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]

参加物

8

反応物 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

生成物 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-one収率 50%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  1. customPurification
  2. washeluting with DCM

出典と根拠

ORDレコード
ord-3151ebb5f83c48eea9ddf3d6aeb4e6fa
出典データセット
uspto-grants-2012_05
特許番号
US08173656B2

関連ノート

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