1-Methylpiperazine → 4-tert-Butyl-N-(3-(6-(4-(1-(isopropyl(methyl)amino)-2-(4-methylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide

HRID 888445Notes

Reaction equation

HRID 888445 reaction equation
[C:1]([C:5]1[CH:44]=[CH:43][C:8]([C:9]([NH:11][C:12]2[C:13]([CH3:42])=[C:14]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:30]=[CH:29][C:28]([CH:31]([N:35]([CH:37]([CH3:39])[CH3:38])[CH3:36])[C:32](O)=[O:33])=[CH:27][CH:26]=4)[C:21](=[O:40])[N:20]([CH3:41])[CH:19]=3)[CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[C:1]([C:5]1[CH:44]=[CH:43][C:8]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:23]=[C:22]([NH:24][C:25]4[CH:26]=[CH:27][C:28]([CH:31]([N:35]([CH:37]([CH3:38])[CH3:39])[CH3:36])[C:32]([N:49]5[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]5)=[O:33])=[CH:29][CH:30]=4)[C:21](=[O:40])[N:20]([CH3:41])[CH:19]=3)[C:13]=2[CH3:42])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 576251502-(4-{6-[3-(4-tert-Butylbenzamido)-2-methylphenyl]-4-methyl-3-oxo-3,4-dihydropyrazin-2-ylamino}phenyl)-2-[isopropyl(methyl)amino]acetic Acid

Product 1

HCID 576251694-tert-Butyl-N-(3-(6-(4-(1-(isopropyl(methyl)amino)-2-(4-methylpiperazin-1-yl)-2-oxoethyl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a sealed tube equipped with a magnetic stirrer, were charged 29 (100 mg, 0.168 mmol), 1-methylpiperazine (14.6 mg, 0.168 mmol), DMF (3 mL), Hunig's base (65.1 mg, 0.503 mmol), and BOP (74.3 mg, 0.168 mmol). The reaction mixture was stirred at room temperature for 26 hrs. Most solvent was removed by rotary evaporation and the resulting residue was dissolved in ethyl acetate (100 mL). The solution was washed with water (15 mL×3), dried over MgSO4, filtered and solvent removed in vacuo. Silica gel column chromatography (MeOH:CH2Cl2=5:95) afforded 30 as a light yellow solid, 25 mg (22%). 1H NMR (300 MHz, CDCl3) 8.45 (s, 1H), 8.09 (s, 1H), 7.95 (s, 1H), 7.92 (s, 1H), 7.85 (m, 2H), 7.75 (m, 1H), 7.54 (s, 1H), 7.51 (s, 1H), 7.40 (m, 2H), 7.19-7.23 (m, 2H), 6.79 (s, 1H), 5.19 (s, 1H), 3.62 (s, 3H), 3.40 (broad s, 2H), 3.21 (broad s, 2H), 2.26-2.50 (m, 9H), 2.18 (s, 3H), 1.92 (broad s, 2H), 1.34 (s, 9H), 1.25-1.31 (m, 6H) ppm; MS (ESI+) m/z 678.19 (M+H).

Workup

  1. customTo a sealed tube equipped with a magnetic stirrer
  2. customMost solvent was removed by rotary evaporation
  3. dissolutionthe resulting residue was dissolved in ethyl acetate (100 mL)
  4. washThe solution was washed with water (15 mL×3)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-2c1399fa19664271add0912e218e4d5d
Source dataset
uspto-grants-2012_08
Patent number
US08247550B2

Reaction notes

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