HCID 58423080, compound → HCID 59023036, compound

HRID 1924955Notes

Reaction equation

HRID 1924955 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:13]=[CH:14][C:15]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[C:16]([CH:20]=2)[C:17]([NH2:19])=[O:18])=[N:4][CH:3]=1.[F:27][C:28]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[C:33]([F:46])[C:29]=1[C:30]([NH2:32])=[O:31]>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>[NH3:4].[C:17]([C:16]1[CH:20]=[C:12]([NH:11][C:5]2[C:6]3[N:7]([CH:8]=[CH:9][N:10]=3)[C:2]([C:35]3[CH:34]=[C:33]([F:46])[C:29]([C:30]([NH2:32])=[O:31])=[C:28]([F:27])[CH:36]=3)=[CH:3][N:4]=2)[CH:13]=[CH:14][C:15]=1[N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)(=[O:18])[NH2:19]

Participants

6

Reactant 2

HCID 58423080HCID 58423080, compoundHCID 59023072HCID 59023072, compound

Product 2

HCID 222AmmoniaHCID 59023036HCID 59023036, compoundYield 41.9%

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-(5-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-2-morpholin-4-yl-benzamide (120 mg, 0.29 mmol), 2,6-difluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzamide (163 mg, 0.58 mmol) 1.5M K2CO3 (1.7 mL, 2.55 mmol), and Pd(PPh3)4 (84 mg, 0.073 mmol) in dioxane (3 mL). Purification by silica gel column chromatography eluting with 98:8 DCM:NH3 (7M in MeOH) affords the title compound as a pale yellow solid (30 mg, 21%). Following the usual procedure, using methanesulfonic acid (0.593 mL), the free base (29.3 mg, 0.060 mmol) is converted into the mesylate salt (27 mg, 99%). LCMS: Rt 2.47 min (98%), m/z (ES+) 494 (M+H)+, 1H-NMR (400 MHz, d6-DMSO) δ (ppm) 2.35 (3H, s, MsOH), 2.97-3.05 (4H, m), 3.74-3.83 (4H, t), 7.35 (1H, d), 7.60-7.65 (4H, m), 7.80 (1H, s), 7.98 (1H, br s), 8.05-8.08 (1H, m), 8.13 (1H, s), 8.26 (1H, br s), 8.50 (1H, d), 8.68 (1H, br s), 10.00 (1H, s).

Workup

  1. customPurification by silica gel column chromatography
  2. washeluting with 98:8 DCM

Sources & evidence

ORD record
ord-d186829703ef4835ae477811542e89ce
Source dataset
uspto-grants-2012_05
Patent number
US08178530B2

Reaction notes

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