Sodium Carbonate → HCID 59375027, compound

HRID 1811176Notes

Reaction equation

HRID 1811176 reaction equation
[CH:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:10](B4OC(C)(C)C(C)(C)O4)=[CH:11][CH:12]=[C:13]([C:18]([NH2:20])=[O:19])[C:14]=3[NH:15]2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].OC(C(F)(F)F)=O.Br[C:38]1[C:39]([CH3:54])=[C:40]([N:44]2[CH:49]=[CH:48][N:47]3[CH:50]=[CH:51][N:52]=[C:46]3[C:45]2=[O:53])[CH:41]=[CH:42][CH:43]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C(CCO)=CC=CC=1.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>[CH:1]([NH:4][C:5]1[CH:17]=[C:16]2[C:8]([C:9]3[C:10]([C:38]4[CH:43]=[CH:42][CH:41]=[C:40]([N:44]5[CH:49]=[CH:48][N:47]6[CH:50]=[CH:51][N:52]=[C:46]6[C:45]5=[O:53])[C:39]=4[CH3:54])=[CH:11][CH:12]=[C:13]([C:18]([NH2:20])=[O:19])[C:14]=3[NH:15]2)=[CH:7][CH:6]=1)([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 66606868HCID 66606868, compoundHCID 86642959HCID 86642959, compound2×

Product 1

HCID 59375027HCID 59375027, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 882672-Methylphenethyl alcoholSolvent

Conditions

Temperature
90 °C

Procedure

Step 2 A suspension of impure 7-(isopropylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide (60 mg, 0.053 mmol), 7-(3-bromo-2-methylphenyl)imidazo[1,2-a]pyrazin-8(7H)-one TFA salt (Intermediate 11-1, 22.3 mg, 0.053 mmol), tetrakis(triphenylphosphine)palladium (3.1 mg, 0.003 mmol) and 2 M aqueous sodium carbonate (0.080 mL, 0.160 mmol) in toluene-ethanol (4:1, 1.3 mL) was heated under nitrogen at 90° C. overnight. The mixture was concentrated and the residue was purified by preparative HPLC. The appropriate effluent fractions were concentrated and the residue was partitioned between NaHCO3 (aq) and EtOAc. The organic phase was dried and concentrated to provide 7-(isopropylamino)-4-(2-methyl-3-(8-oxoimidazo[1,2-a]pyrazin-7(8H)-yl)phenyl)-9H-carbazole-1-carboxamide as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 10.83-10.99 (1H, m), 8.01 (1H, br. s.), 7.83 (1H, dd, J=4.5, 1.0 Hz), 7.68-7.77 (1H, m), 7.59-7.67 (1H, m), 7.38-7.50 (3H, m), 7.24-7.38 (2H, m), 7.08 (1H, dd, J=8.4, 5.9 Hz), 6.76-6.87 (1.55H, m), 6.73 (1H, dd, J=7.4, 1.9 Hz), 6.48 (0.45; H, d, J=8.8 Hz), 6.13-6.29 (1H, m), 5.44 (1H, t, J=8.3 Hz), 3.40-3.55 (1H, m), 1.70 (3H, d, J=11.4 Hz), 1.09 (6H, td, J=5.8, 3.4 Hz). Mass spectrum m/z 491.3 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue was purified by preparative HPLC
  3. concentrationThe appropriate effluent fractions were concentrated
  4. customthe residue was partitioned between NaHCO3 (aq) and EtOAc
  5. customThe organic phase was dried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-abdf2a5b4ac640c7a47422d6d80236a1
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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