Potassium Hydroxide → HCID 5275992, compound

HRID 1788530Notes

Reaction equation

HRID 1788530 reaction equation
C[O:2][C:3]([C:5]1[CH:38]=[CH:37][C:8]2[N:9]([CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[C:17]([C:22]3[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:23]=3Br)[CH:16]=[CH:15]4)=[N:11][C:7]=2[CH:6]=1)=[O:4].[F:39][C:40]1[CH:45]=[CH:44][C:43](B(O)O)=[CH:42][C:41]=1[Cl:49].C(=O)(O)[O-].[Na+].[OH-].[K+]>C1(C)C=CC=CC=1.CO.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>[Cl:49][C:41]1[CH:42]=[C:43]([CH:44]=[CH:45][C:40]=1[F:39])[C:23]1[C:22]([C:17]2[CH:16]=[CH:15][C:14]3[C:19](=[CH:20][CH:21]=[C:12]([C:10]4[N:9]([CH:31]5[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]5)[C:8]5[CH:37]=[CH:38][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]=5[N:11]=4)[CH:13]=3)[N:18]=2)=[CH:27][C:26]([O:28][CH3:29])=[CH:25][CH:24]=1

Participants

9

Reactant 4

HCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 68922215HCID 68922215, compound

Product 1

HCID 5275992HCID 5275992, compoundYield 7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

In dried vial with a Teflon lined screw cap, a solution of Compound 365b (100 mg, 0.175 mmol), 4-fluoro-3-chlorophenylboronic acid (61 mg, 0.2625 mmol), and Palladium Tetrakis (20 mg, 0.0175 mmol) in toluene (6.5 mL), methanol (1.6 mL), and saturated sodium bicarbonate in water (800 ul) was degassed, flushed with argon, and sealed. The reaction was stirred for 16 hours at 90° C. The vial was then cooled to room temperature and 10% w/v KOH in methanol (2 mL, 3.5 mmol) was added. The reaction was resealed and stirred at 70° C. for 1 hour. The completed reaction was then evaporated to dryness, purified via HPLC, and converted to the HCl salt using the standard procedure (as described for Compound 516) to produce the title compound (7 mg, 7% yield).

Workup

  1. customflushed with argon
  2. customsealed
  3. temperatureThe vial was then cooled to room temperature
  4. additionwas added
  5. stirringstirred at 70° C. for 1 hour
  6. customThe completed reaction
  7. customwas then evaporated to dryness
  8. custompurified via HPLC

Sources & evidence

ORD record
ord-f7ff849513b44655869091b850785528
Source dataset
uspto-grants-2009_03
Patent number
US07511145B2

Reaction notes

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