Water → HCID 86658766, compound

HRID 1396182Notes

Reaction equation

HRID 1396182 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[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[F:26][C:27]1[N:32]=[C:31]([N:33]([C:41]2[CH:42]=[N:43][C:44]([CH3:47])=[CH:45][CH:46]=2)[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:30]=[CH:29][C:28]=1[CH:48]=[O:49].O>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([Cl:19])[C:13]=3[C:12]([CH:48]([OH:49])[C:28]3[CH:29]=[CH:30][C:31]([N:33]([C:41]4[CH:42]=[N:43][C:44]([CH3:47])=[CH:45][CH:46]=4)[C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[N:32][C:27]=3[F:26])=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 22484500HCID 22484500, compoundHCID 58485771HCID 58485771, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 86658766HCID 86658766, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a solution of 7-(benzenesulfonyl)-4-chloro-5-iodo-pyrrolo[2,3-d]pyrimidine (1, 0.43 g, 1.01 mmol) in Tetrahydrofuran (5 mL) at −30° C. under nitrogen was added 2.0 M Isopropylmagnesium Chloride in Tetrahydrofuran (0.5 ml) slowly. The reaction was allowed to warm to −5° C. in 75 minutes. Then, the reaction was cooled to −45° C., followed by adding tert-butyl N-(6-fluoro-5-formyl-2-pyridyl)-N-(6-methyl-3-pyridyl)carbamate (84, 0.24 g, 0.72 mmol) in THF (3.0 mL). The reaction was allowed to warm to room temperature in around 2 hours. The reaction was poured in to water, extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated, purified with silica gel column chromatography eluting with 20%-100% ethyl acetate in hexane to give product (85, 0.41 g, 90.6%). MS (ESI) [M+H+]+=625.0.

Workup

  1. temperatureThen, the reaction was cooled to −45° C.
  2. temperatureto warm to room temperature in around 2 hours
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. custompurified with silica gel column chromatography
  8. washeluting with 20%-100% ethyl acetate in hexane
  9. customto give product (85, 0.41 g, 90.6%)

Sources & evidence

ORD record
ord-92fb8daba8524ffaaf89888d39e1509f
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

Loading…