Water → HCID 58485824, compound

HRID 1396174Notes

Reaction equation

HRID 1396174 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([CH:19]4[CH2:21][CH2:20]4)[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.[C:28]([O:32][C:33](=[O:52])[N:34]([C:43]1[CH:48]=[CH:47][C:46]([CH:49]=[O:50])=[C:45]([F:51])[N:44]=1)[C:35]1[CH:36]=[N:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=1)([CH3:31])([CH3:30])[CH3:29].O>O1CCCC1>[C:28]([O:32][C:33](=[O:52])[N:34]([C:43]1[CH:48]=[CH:47][C:46]([CH:49]([C:12]2[C:13]3[C:18]([CH:19]4[CH2:21][CH2:20]4)=[N:17][CH:16]=[N:15][C:14]=3[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:11]=2)[OH:50])=[C:45]([F:51])[N:44]=1)[C:35]1[CH:36]=[N:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=1)([CH3:31])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 962WaterHCID 58485695HCID 58485695, compoundHCID 58485698HCID 58485698, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 58485824HCID 58485824, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of 7-benzenesulfonyl-4-cyclopropyl-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (32, 0.760 g, 1.79 mmol) in 5.43 mL of tetrahydrofuran at −40° C. under nitrogen, isopropylmagnesium chloride (0.892 mL, 2.0 M in tetrahydrofuran, 1.78 mmol) is added slowly. The reaction is allowed to warm to −5° C. over 75 minutes, then cooled to −45° C. and (6-fluoro-5-formyl-pyridin-2-yl)-(6-methoxy-pyridin-3-yl)-carbamic acid tert-butyl ester (57, 0.38 g, 1.1 mmol) in 2.0 mL of tetrahydrofuran is added. The reaction is allowed to warm to room temperature over 2 hours, then poured into water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography, eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (75, 0.64 g). MS (ESI) [M+H+]+=647.2.

Workup

  1. temperaturecooled to −45° C.
  2. temperatureto warm to room temperature over 2 hours
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material is purified by silica gel column chromatography
  8. washeluting with 20-100% ethyl acetate in hexane
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-293f84b37e5a48e1af2da3ff24a1f513
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

Loading…