Toluene → 3-(3-chloro-4-fluorophenyl)-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide

HRID 2410930Notes

Reaction equation

HRID 2410930 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[C:9]([C:15]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[O:16])[CH:8]=3.[Cl:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][C:32]=1[F:33].C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:26][C:27]1[CH:28]=[C:29]([C:2]2[CH:3]=[C:4]([C:23]([NH2:25])=[O:24])[C:5]3[NH:6][C:7]4[C:12]([C:13]=3[CH:14]=2)=[CH:11][CH:10]=[C:9]([C:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])[CH:8]=4)[CH:30]=[CH:31][C:32]=1[F:33]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 666047593-bromo-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide

Product 1

HCID 666053693-(3-chloro-4-fluorophenyl)-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamideYield 17.7%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
160 °C

Procedure

3-Bromo-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide (33 mg, 0.075 mmol, Example 144A) was dissolved in MeOH (0.6 mL) and added into a microwave vial containing 3-chloro-4-fluorophenylboronic acid (55.7 mg, 0.32 mmol), followed by addition of Na2CO3 (0.12 mL of a 2M aq. solution) and PdCl2(dppf)-CH2Cl2 (6.12 mg, 7.50 μmol) and Toluene (1.2 mL). The vial was sealed and heated in a BIOTAGE® microwave reactor for 15 minutes at 160° C. The reaction mixture was evaporated to dryness, dissolved in DMF+isopropanol and purified by preparative HPLC. Product containing fractions were combined and evaporated to dryness to give 6.0 mg 3-(3-chloro-4-fluorophenyl)-7-(morpholine-4-carbonyl)-9H-carbazole-1-carboxamide. HPLC retention time 4.72 min. (SUPELCO® Ascentis Express 4.6×50 mm 2.7 um C18, 2 ml/min, 0 to 100% B in 8 minutes, then 100% B for 1 minute. Solvent A: 5% CH3CN—95% H2O—10 mM NH4OAc; Solvent B: 95% CH3CN—5% H2O—10 mM NH4OAc). MS (ESI) m/e+=452 [M+H]+.

Workup

  1. additionadded into a microwave vial
  2. customThe vial was sealed
  3. customThe reaction mixture was evaporated to dryness
  4. dissolutiondissolved in DMF+isopropanol
  5. custompurified by preparative HPLC
  6. additionProduct containing fractions
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-7725b11664b94c57bdcec0f811fc59f1
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

Loading…