Water → HCID 57963099, compound

HRID 1775166Notes

Reaction equation

HRID 1775166 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([O:19][CH3:20])[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:27]([O:31][C:32](=[O:51])[N:33]([CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[Cl:50])[C:34]1[CH:39]=[CH:38][C:37]([CH:40]=[O:41])=[C:36]([F:42])[N:35]=1)([CH3:30])([CH3:29])[CH3:28].O>O1CCCC1>[C:27]([O:31][C:32](=[O:51])[N:33]([C:34]1[CH:39]=[CH:38][C:37]([CH:40]([C:12]2[C:13]3[C:18]([O:19][CH3:20])=[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:41])=[C:36]([F:42])[N:35]=1)[CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=1[Cl:50])([CH3:30])([CH3:28])[CH3:29]

Participants

6

Reactant 4

HCID 962WaterHCID 57963053HCID 57963053, compoundHCID 57963111HCID 57963111, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57963099HCID 57963099, compoundYield 92.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 7-benzenesulfonyl-5-iodo-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (42, 0.408 g, 0.983 mmol) in 4.0 mL of tetrahydrofuran at −50° C. under an atmosphere of nitrogen, isopropylmagnesium chloride (0.500 mL, 2.00 M in tetrahydrofuran, 1.00 mmol) was added slowly. The reaction was allowed to warm to 5° C. over 70 minutes, cooled to −45° C. and (2-chloro-benzyl)-(6-fluoro-5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (19, 0.240 g, 0.658 mmol) in 2.0 mL of tetrahydrofuran was added. The reaction was allowed to warm to room temperature over an hour, then poured into water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (44, 0.400 g).

Workup

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

Sources & evidence

ORD record
ord-ca097f86e26442099d88cf443d2cdf60
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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