Potassium Carbonate → tert-butyl 4-(4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2375821Notes

Reaction equation

HRID 2375821 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([Cl:19])[C:13]=3[CH:12]=[C:11]2I)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:21]([O:25][C:26]([N:28]1[CH2:29][CH:30]=[C:31]([C:11]2[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[C:14]3[N:15]=[CH:16][N:17]=[C:18]([Cl:19])[C:13]=3[CH:12]=2)[CH2:32][CH2:33]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 574158854-Chloro-6-iodo-7-phenylsulfonyl-7H-pyrrolo[2,3-D]pyrimidine

Product 1

HCID 58709981tert-butyl 4-(4-chloro-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

7-Benzenesulfonyl-4-chloro-6-iodo-7H-pyrrolo[2,3-d]pyrimidine (4.05 g, 9.65 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (2.985 g, 9.65 mmol), potassium carbonate (2.935 g, 21.25 mmol) and dichlorobis(triphenylphosphine)-palladium(II) (678 mg, 0.96 mmol) were combined in dioxane/water (85 mL:21 mL) and heated to 90° C. for 2 h. After cooling the reaction mixture was extracted with ethyl acetate (3×50 mL), the organic layers were combined and washed with aqueous sodium bicarbonate, brine and finally water. The organic layer was dried over anhydrous magnesium sulphate, filtered and pre-absorbed onto silica in vacuo. Purification on silica gel by gradient elution with isohexane:ethyl acetate (6:1) finishing with isohexane:ethyl acetate (4:1) yielded a yellow solid. 1H NMR (d6-DMSO, 400 MHz) 8.8(1H, s), 8.0 (2H, d), 7.8(1H,m), 7.6(2H,m), 6.8(1H, s), 6.0(1H, s), 4.1(2H, br. s), 3.6(2H,m), 2.5(2H, br. s), and 1.5(9H, s); LC/MS: m/z 474 [M+H]+, Rt=4.42 min

Workup

  1. temperatureAfter cooling the reaction mixture
  2. extractionwas extracted with ethyl acetate (3×50 mL)
  3. washwashed with aqueous sodium bicarbonate, brine and finally water
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. custompre-absorbed onto silica in vacuo
  7. customPurification on silica gel
  8. washby gradient elution with isohexane:ethyl acetate (6:1)
  9. customyielded a yellow solid

Sources & evidence

ORD record
ord-ceb1f4f6d0eb43d7adb269b1583ebf9c
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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