4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → N-(2-Diethylamino-ethyl)-4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-benzamide

HRID 1924887Notes

Reaction equation

HRID 1924887 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:27]=[CH:26][C:15]([C:16]([NH:18][CH2:19][CH2:20][N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])=[O:17])=[CH:14][CH:13]=2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[N:38][NH:39][CH:40]=2)O1.CC([O-])(C)C.[Na+]>CN(C=O)C.O.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].[CH2:22]([N:21]([CH2:24][CH3:25])[CH2:20][CH2:19][NH:18][C:16](=[O:17])[C:15]1[CH:26]=[CH:27][C:12]([NH:11][C:5]2[C:6]3[N:7]([CH:8]=[CH:9][N:10]=3)[C:2]([C:36]3[CH:37]=[N:38][NH:39][CH:40]=3)=[CH:3][N:4]=2)=[CH:13][CH:14]=1)[CH3:23]

Participants

7

Reactant 3

HCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 23676156Sodium t-butoxideHCID 590230454-(5-Bromo-imidazo[1,2-a]pyrazin-8-ylamino)-N-(2-diethylamino-ethyl)-benzamide

Product 2

HCID 222AmmoniaHCID 24856764N-(2-Diethylamino-ethyl)-4-[5-(1H-pyrazol-4-yl)-imidazo[1,2-a]pyrazin-8-ylamino]-benzamideYield 139.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

In the same way as described for Compound 85, step 1, using 4-(5-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-N-(2-diethylamino-ethyl)-benzamide (0.12 g, 0.28 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (65 mg, 0.33 mmol), Pd(PPh3)4 (32 mg, 0.028 mmol) and NaOtBu (0.11 g, 1.11 mmol) in DMF/water. Purification by silica gel column chromatography eluting with 92:8 DCM:NH3 (7M in MeOH) affords the title compound (0.0815 g, 70%). LCMS Rt 1.93 min (99%), m/z (APCI) 419 (M+H)+; 1H-NMR (400 MHz, d6-DMSO) δ(ppm) 0.82-0.95 (6H, t), 1.64 (2H, s), 2.37-2.43 (2H, m), 3.17-3.22 (4H, m), 6.55 (1H, br s), 7.20 (1H, br s), 7.55 (1H, s), 7.65-7.69 (3H, m), 7.98-8.09 (4H, m), 9.67 (1H, s), 13.30 (1H, br s).

Workup

  1. customPurification by silica gel column chromatography
  2. washeluting with 92:8 DCM

Sources & evidence

ORD record
ord-7542b90502ba4642981544851542db2b
Source dataset
uspto-grants-2012_05
Patent number
US08178530B2

Reaction notes

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