Sodium Carbonate → 5-[2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-nicotinic acid

HRID 1878610Notes

Reaction equation

HRID 1878610 reaction equation
Cl[C:2]1[C:3]2[CH:17]=[CH:16][NH:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[N:7]=1.C([O:20][C:21]([C:23]1[CH:24]=[N:25][CH:26]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:28]=1)=[O:22])C.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>COCCOC.CCO.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.O.C(O)(=O)C>[CH3:14][C:10]1[N:9]=[C:8]([C:6]2[N:7]=[C:2]([C:27]3[CH:26]=[N:25][CH:24]=[C:23]([CH:28]=3)[C:21]([OH:22])=[O:20])[C:3]3[CH:17]=[CH:16][NH:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 3816953Ethyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carboxylateHCID 866324284-chloro-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine2×

Product 1

HCID 687615905-[2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-nicotinic acid

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 20074477Dimethoxyethane ethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-chloro-2-(6-methyl-pyridin-2-yl)-7H-pyrrolo[2,3-d]pyrimidine (Intermediate 2) (1 eq, 1.94 mmol, 500 mg) and 3-ethoxycarbonylpyridine-5-boronic acid pinacol ester (Frontier Scientific, Logan, USA) (1.5. eq, 2.91 mmol, 820 mg) in DME/EtOH (1:1, 6 ml), aqueous Na2CO3 solution (2 M, 3 eq, 5.80 mmol, 2.9 ml) and Pd(PPh3)4 (0.05 eq, 0.097 mmol, 116 mg) are added. The resulting mixture is heated using microwave radiation at 120° C. for 20 min. The solvents are evaporated and the remaining residue is suspended in MeOH (30 ml). The mixture is cooled to 0° C., then aqueous NaOH solution (1 M, 1.9 eq, 3.60 mmol, 3.6 ml) is added. After stirring for 10 min at this temperature, the mixture is allowed to warm up to r.t. and stirred for another 1 h. After cooling down to 0° C., glacial acetic acid (5 ml) and water (100 ml) are added. The resulting precipitate is filtered and washed with water giving the title compound; [M+H]+=332.

Workup

  1. temperatureThe resulting mixture is heated
  2. customat 120° C.
  3. customfor 20 min
  4. customThe solvents are evaporated
  5. temperatureto warm up to r.t.
  6. stirringstirred for another 1 h
  7. temperatureAfter cooling down to 0° C.
  8. filtrationThe resulting precipitate is filtered
  9. washwashed with water giving the title compound

Sources & evidence

ORD record
ord-739670f2c34d4ebcab9bb69273181012
Source dataset
uspto-grants-2012_11
Patent number
US08314112B2

Reaction notes

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