Hydrochloric Acid → HCID 67440498, compound

HRID 1471514Notes

Reaction equation

HRID 1471514 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([B:21]3OC(C)(C)C(C)(C)[O:22]3)=[C:17]([CH:30]=[O:31])[CH:16]=2)[N:7]=1)=[O:5])[CH3:2].[BH4-].[Na+].Cl>CO>[CH2:1]([O:3][C:4]([C:6]1[C:11]([C:12]#[N:13])=[CH:10][CH:9]=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]3[B:21]([OH:22])[O:31][CH2:30][C:17]=3[CH:16]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 86707698HCID 86707698, compound

Product 1

HCID 67440498HCID 67440498, compoundYield 107.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-cyano-6-[3-formyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-pyridine-2-carboxylic acid ethyl ester (25, 0.11 g, 0.23 mmol) in methanol (5 mL) was added sodium borohydride (0.01 g, 0.27 mmol) at 0° C. After 1 h at 0° C., 2 M HCl was added until pH is 2˜3. The solvent was removed under reduced pressure to give crude product, which was purified by reverse phase prep HPLC using CH3CN/H2O (0.1% AcOH) as the eluent to yield the title compound (D45) (0.08 g, 20%) as a white solid after lyophilization. Mp 204-206° C. 1H NMR 400 MHz (DMSO-d6) δ: 9.26 (s, 1H), 8.47 (d, J=9.0 Hz, 1H), 7.80 (d, J=9.4 Hz, 1H), 7.39 (d, J=8.6 Hz, 1H), 7.32 (s, 1H), 7.24-7.19 (m, 1H), 4.99 (s, 2H), 4.32-4.23 (m, 2H), 1.39-1.20 (m, 3H); MS (ES) m/z: 325 (M+1)+; HPLC purity: 96.01% (Maxplot), 98.13% (220 nm), 97.47% (254 nm).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto give crude product, which
  3. customwas purified by reverse phase prep HPLC

Sources & evidence

ORD record
ord-9a1928ad165f4a25accf72fd29b0012a
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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