Water → HCID 58485758, compound

HRID 1396180Notes

Reaction equation

HRID 1396180 reaction equation
[CH:1]1([C:4]2[C:5]3[C:12](I)=[CH:11][N:10]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:17])[CH3:16])[C:6]=3[N:7]=[CH:8][N:9]=2)[CH2:3][CH2:2]1.C([Mg]Cl)(C)C.[C:29]([O:33][C:34](=[O:52])[N:35]([C:45]1[CH:46]=[N:47][C:48]([Cl:51])=[CH:49][CH:50]=1)[C:36]1[CH:41]=[CH:40][C:39]([CH:42]=[O:43])=[C:38]([F:44])[N:37]=1)([CH3:32])([CH3:31])[CH3:30].O>O1CCCC1>[C:29]([O:33][C:34](=[O:52])[N:35]([C:45]1[CH:46]=[N:47][C:48]([Cl:51])=[CH:49][CH:50]=1)[C:36]1[CH:41]=[CH:40][C:39]([CH:42]([C:12]2[C:5]3[C:4]([CH:1]4[CH2:2][CH2:3]4)=[N:9][CH:8]=[N:7][C:6]=3[N:10]([Si:14]([CH:21]([CH3:23])[CH3:22])([CH:18]([CH3:20])[CH3:19])[CH:15]([CH3:16])[CH3:17])[CH:11]=2)[OH:43])=[C:38]([F:44])[N:37]=1)([CH3:32])([CH3:30])[CH3:31]

Participants

6

Reactant 4

HCID 962WaterHCID 58485679HCID 58485679, compoundHCID 58485865HCID 58485865, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 58485758HCID 58485758, compoundYield 55.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-5 °C

Procedure

To 4-cyclopropyl-5-iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (19, 0.72 g, 1.64 mmol) in 6.0 mL of tetrahydrofuran at −40° C. under nitrogen, isopropylmagnesium chloride (0.82 mL, 2.01 M in tetrahydrofuran, 1.65 mmol) is added slowly. The reaction is allowed to warm to −5° C. in 75 minutes, then cooled to −45° C. and (6-chloro-pyridin-3-yl)-(6-fluoro-5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (80, 0.48 g, 1.38 mmol) in 5.0 mL is added. The reaction is allowed to warm to room temperature in 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 (81, 0.51 g). MS (ESI) [M+H+]+=667.2).

Workup

  1. temperaturecooled to −45° C.
  2. temperatureto warm to room temperature in 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-8f7c9d74f5aa457097b1c511eafc34d0
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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