Water → HCID 86716126, compound

HRID 627558Notes

Reaction equation

HRID 627558 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:20]3[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=3)([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([N:26]([CH2:29][CH3:30])[CH2:27][CH3:28])[C:3]=1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38].CB1OB(C)OB(C)O1.C([O-])([O-])=O.[K+].[K+].O.[NH4+].[Cl-]>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.O1CCOCC1.COCCOC>[CH2:29]([N:26]([CH2:27][CH3:28])[C:4]1[C:3]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[C:2]([CH3:37])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:20]3[N:24]([CH3:25])[CH:23]=[N:22][CH:21]=3)([C:14]3[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=1)[CH3:30].[C:37]([OH:43])([C:39]([F:42])([F:41])[F:40])=[O:38]

Participants

9

Reactant 5

HCID 962Water2×HCID 11430Potassium Carbonate2×HCID 25517Ammonium ChlorideHCID 574072TrimethylboroxineHCID 86716128HCID 86716128, compound

Product 1

HCID 86716126HCID 86716126, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A sealed tube containing [4-chloro-2-(diethylamino)-3-phenylquinolin-6-yl](1-methyl-1H-imidazol-5-yl)pyridin-4-ylmethanol•TFA (21 mg, 0.029 mmol, Example 99), Pd(PPh3)4 (5.0 mg, 0.0043 mmol), 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane (0.010 mL, 0.072 mmol), 2.0 M K2CO3 in water (0.050 mL, 0.10 mmol), and 1,2-dimethoxyethane (1.2 mL) was bubbled with N2 for 3 min. After heating at 90° C. for 17 hours, more Pd(PPh3)4 (5.0 mg, 0.0043 mmol), 2.0 M K2CO3 in water (0.040 mL, 0.080 mmol), and 1,4-dioxane (1 mL) were added. The mixture was heated at 130° C. for 16 hours. NH4Cl (aqueous) was added, the organic layer was separated, and the aqueous layer was extracted with CH2Cl2. The combined organic phases were dried (Na2SO4), filtered, concentrated, and purified by reverse phase HPLC (water/acetonitrile/0.1% TFA) to give the title compound. 1H NMR (400 MHz, MeOH-d4) δ 9.06 (s, 1H), 8.79 (d, J=6.57 Hz, 2H), 8.25 (d, J=2.02 Hz, 1H), 8.14 (d, J=9.09 Hz, 1H), 7.94 (d, J=6.57 Hz, 2H), 7.88 (dd, J=2.02, 9.09 Hz, 1H), 7.51-7.64 (m, 3H), 7.40 (d, J=6.57 Hz, 2H), 7.20 (s, 1H), 3.69 (s, 3H), 3.46 (q, J=7.07 Hz, 4H), 2.41 (s, 3H), 1.04 (t, J=7.07 Hz, 6H); MS m/e 478.0 [M+H]+.

Workup

  1. customwas bubbled with N2 for 3 min
  2. temperatureThe mixture was heated at 130° C. for 16 hours
  3. customthe organic layer was separated
  4. extractionthe aqueous layer was extracted with CH2Cl2
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by reverse phase HPLC (water/acetonitrile/0.1% TFA)

Sources & evidence

ORD record
ord-eaafc6b0e4cd4997bf373d136a48f24c
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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