Hydrochloric Acid → HCID 89541653, compound

HRID 1504326Notes

Reaction equation

HRID 1504326 reaction equation
Br[C:2]1[C:7]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:6][C:5]([NH:13][C:14](=[O:34])[C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:23][C@H:22]3[CH3:33])=[N:17][CH:16]=2)=[C:4]([Cl:35])[CH:3]=1.O1CCCC1.[B:41](OC)([O:44]C)[O:42]C.Cl>O.C(O)C>[Cl:35][C:4]1[C:5]([NH:13][C:14](=[O:34])[C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][N:24]([C:27](=[O:32])[C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:23][C@H:22]3[CH3:33])=[N:17][CH:16]=2)=[CH:6][C:7]([O:8][C:9]([F:11])([F:12])[F:10])=[C:2]([B:41]([OH:44])[OH:42])[CH:3]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2×HCID 8470Trimethyl borateHCID 89541530HCID 89541530, compound

Product 1

HCID 89541653HCID 89541653, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Under an atmosphere of nitrogen, a mixture of N-(4-bromo-2-chloro-5-trifluoromethoxy-phenyl)-6-[(R)-4-(2,2-dimethyl-propionyl)-2-methyl-piperazin-1-yl]-nicotinamide (20.0 g, 34.6 mmol) and tetrahydrofuran (200 mL) was cooled to 0° C. and then 1.3 M isopropylmagnesium chloride lithium chloride complex in tetrahydrofuran (79.9 mL, 104 mmol) was added dropwise at 0-10° C. After 2.5 h, boric acid, trimethyl ester (12.0 mL, 106 mmol) was added dropwise, and then 1 N HCl (105 mL) was added and the reaction mixture was stirred overnight. The reaction mixture was extracted with EtOAc (250 mL); the organic layer was washed with water, sat. aq. NaHCO3, dried over MgSO4, and evaporated to give crude product (22.8 g). To the crude product was added ethanol (230 mL) and then slowly water (57.5 mL). The resulting mixture was stirred for 10 days and filtered to give the title intermediate as a crystalline solid (10.7 g, 57% yield).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (250 mL)
  2. washthe organic layer was washed with water, sat. aq. NaHCO3
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customto give crude product (22.8 g)
  6. stirringThe resulting mixture was stirred for 10 days
  7. filtrationfiltered

Sources & evidence

ORD record
ord-4cda94daa19547999a3a16d50a9151d1
Source dataset
uspto-grants-2015_12
Patent number
US09212168B2

Reaction notes

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