Hydrochloric Acid → HCID 59416017, compound

HRID 2061816Notes

Reaction equation

HRID 2061816 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([C:13]2[S:14][CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=2)[C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][N:8]=1)=[O:5])[CH3:2].[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH:39]1[CH2:44][N:45]1[C:54]2[C:49](=[CH:50][C:51](I)=[CH:52][CH:53]=2)[C:48](=[O:56])[C:47]([C:57]([O:59]CC)=[O:58])=[CH:46]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C([O-])([O-])=O.[Cs+].[Cs+].Cl>O1CCOCC1.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.CO>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH:39]1[CH2:44][N:45]1[C:54]2[C:49](=[CH:50][C:51]([C:10]3[CH:9]=[N:8][C:7]([NH:6][C:4]([NH:3][CH2:1][CH3:2])=[O:5])=[CH:12][C:11]=3[C:13]3[S:14][CH:15]=[C:16]([C:18]([F:19])([F:20])[F:21])[N:17]=3)=[CH:52][CH:53]=2)[C:48](=[O:56])[C:47]([C:57]([OH:59])=[O:58])=[CH:46]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 592084681-Ethyl-3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-2-yl)urea2×HCID 59416130HCID 59416130, compound2×

Product 1

HCID 59416017HCID 59416017, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-(3-Ethylureido)-4-(4-(trifluoromethyl)thiazol-2-yl)pyridin-3-ylboronic acid (Intermediate 17, 0.448 g, 1.24 mmol) and ethyl 1-((1-(tert-butoxycarbonyl)piperidin-2-yl)methyl)-6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (Intermediate 72, 0.672 g, 1.24 mmol) were combined and diluted with dioxane (6 mL). A solution of Cs2CO3 (0.689 g, 2.11 mmol) in water (1.5 mL) was added. Tetrakis(triphenylphosphine)palladium(0) (0.144 g, 0.12 mmol) was added. The mixture was heated at 100° C. overnight. After cooling to RT, water and MeOH were added and the mixture was conconcentrated in vacuo. The residue was acidified with 1 N aq HCl and then dried on a lyophilizer. The resultant solid with diluted with EtOAc and water and the layers were separated. The organic layer was washed with water, brine, dried over Na2SO4 and conconcentrated in vacuo to give the title compound which was used without further purification.

Workup

  1. temperatureAfter cooling to RT
  2. customdried on a lyophilizer
  3. additionThe resultant solid with diluted with EtOAc and water
  4. customthe layers were separated
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-8dc224dfa3524158a7b3c6ed05cadbfa
Source dataset
uspto-grants-2012_10
Patent number
US08283361B2

Reaction notes

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