Cesium carbonate → HCID 59145171, compound

HRID 1094746Notes

Reaction equation

HRID 1094746 reaction equation
[F:1][C:2]1[C:3]([C:9]2[N:10]([CH:15]([CH3:17])[CH3:16])[C:11]([CH3:14])=[N:12][CH:13]=2)=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.C[O:19][C:20]([C:22]1[S:23][C:24](Br)=[CH:25][CH:26]=1)=[O:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O1CCOCC1.C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:1][C:2]1[C:3]([C:9]2[N:10]([CH:15]([CH3:17])[CH3:16])[C:11]([CH3:14])=[N:12][CH:13]=2)=[N:4][C:5]([NH:8][C:24]2[S:23][C:22]([C:20]([OH:21])=[O:19])=[CH:26][CH:25]=2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 605713Methyl 5-bromothiophene-2-carboxylateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59799439HCID 59799439, compound

Product 1

HCID 59145171HCID 59145171, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolventHCID 22018518Dioxane tetrahydrofuranSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of the above amine (235 mg, 1.71 mmol), 5-bromo-thiophene-2-carboxylic acid methyl ester (565 mg, 2.56 mmol), Pd2(dba)3 (31 mg, 0.03 mmol), XantPhos (49 mg, 0.09 mmol) and Cs2CO3 (1.1 g, 3.42 mmol) in dioxane was heated in a pressure vessel at 130° C. After 13 hours, the reaction mixture was diluted with dioxane/THF (1:1, 40 mL) and stirred. The mixture was then filtered through celite pad and washed with DCM/THF. The filtrate was then concentrated and used further without purification. MS found for C17H18FN5O2S as (M+H)+ 376.15. To the above crude ester in MeOH/THF (1:1) (10 mL) was added 3N NaOH (4.0 mL) and stirred at 55° C. After 16 hours, the reaction mixture was concentrated, diluted with water and washed with ether (3×). The aqueous phase was then neutralized with 6N HCl (1.5 mL) and the precipitated solid was dried to give 5-[5-fluoro-4-(3-isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-thiophene-2-carboxylic acid which was used for the next step without purification. MS found for C16H16FN5O2S as (M+H)+ 362.07.

Workup

  1. filtrationThe mixture was then filtered through celite pad
  2. washwashed with DCM/THF
  3. concentrationThe filtrate was then concentrated
  4. customused further without purification
  5. additionTo the above crude ester in MeOH/THF (1:1) (10 mL) was added 3N NaOH (4.0 mL)
  6. stirringstirred at 55° C
  7. waitAfter 16 hours
  8. concentrationthe reaction mixture was concentrated
  9. additiondiluted with water
  10. washwashed with ether (3×)
  11. customthe precipitated solid was dried

Sources & evidence

ORD record
ord-f5f5e915b51945f4908cafc10257bf4d
Source dataset
uspto-grants-2012_03
Patent number
US08134000B2

Reaction notes

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