Sodium Carbonate → HCID 59375086, compound

HRID 1811177Notes

Reaction equation

HRID 1811177 reaction equation
[OH:1][C:2]([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)([CH3:4])[CH3:3].Br[C:31]1[C:32]([CH3:49])=[C:33]([NH:37][C:38]2[C:47]3[C:42](=[C:43]([F:48])[CH:44]=[CH:45][CH:46]=3)[N:41]=[CH:40][N:39]=2)[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[F:48][C:43]1[CH:44]=[CH:45][CH:46]=[C:47]2[C:42]=1[N:41]=[CH:40][N:39]=[C:38]2[NH:37][C:33]1[C:32]([CH3:49])=[C:31]([C:10]2[C:9]3[C:8]4[C:16](=[CH:17][C:5]([C:2]([OH:1])([CH3:4])[CH3:3])=[CH:6][CH:7]=4)[NH:15][C:14]=3[C:13]([C:18]([NH2:20])=[O:19])=[CH:12][CH:11]=2)[CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66606234HCID 66606234, compound2×HCID 66606464HCID 66606464, compound

Product 1

HCID 59375086HCID 59375086, compoundYield 65.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Step 2 A mixture of 7-(2-hydroxypropan-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole-1-carboxamide (ca. 60% purity, 35 mg, 0.053 mmol), N-(3-bromo-2-methylphenyl)-8-fluoroquinazolin-4-amine (Intermediate 32-7, 17.69 mg, 0.053 mmol), and 2 M aqueous sodium carbonate (0.067 mL, 0.133 mmol) in toluene (0.8 mL) and ethanol (0.200 mL) was purged with argon, treated with tetrakis(triphenylphosphine)palladium (3.1 mg, 0.003 mmol) and heated at 90° C. in a sealed tube for 16.5 h. The mixture was cooled to rt and concentrated. The residue was purified by preparative HPLC and the appropriate effluent fractions were treated with NaHCO3 (aq) and partially concentrated at rt. The resulting aqueous suspension was filtered and the precipitate was washed with water and dried to provide 4-(3-(8-fluoroquinazolin-4-ylamino)-2-methylphenyl)-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide as a white solid (18.0 mg, 61%). 1H NMR (400 MHz, DMSO-d6) δ 11.41 (1H, s), 10.08 (1H, s), 8.56 (1H, s), 8.35 (1H, d, J=8.4 Hz), 8.16 (1H, br. s.), 7.99 (1H, d, J=7.9 Hz), 7.87 (1H, s), 7.70 (1H, dd, J=10.2, 8.3 Hz), 7.60 (1H, td, J=8.1, 5.2 Hz), 7.42-7.54 (3H, m), 7.28 (1H, dd, J=7.3, 1.3 Hz), 7.11 (2H, s), 7.01 (1H, d, J=7.7 Hz), 5.00 (1H, s), 1.85 (3H, s), 1.49 (6H, s). Mass spectrum m/z 520.1 (M+H)+.

Workup

  1. customwas purged with argon
  2. temperatureThe mixture was cooled to rt
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC
  5. additionthe appropriate effluent fractions were treated with NaHCO3 (aq)
  6. concentrationpartially concentrated at rt
  7. filtrationThe resulting aqueous suspension was filtered
  8. washthe precipitate was washed with water
  9. customdried

Sources & evidence

ORD record
ord-11ce35fc13b54db4b99c0171c8e31db1
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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