Ammonium Chloride → (2-methylsulfanyl-pyrimidin-5-yl)-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanol

HRID 1775175Notes

Reaction equation

HRID 1775175 reaction equation
I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[CH3:26][S:27][C:28]1[N:33]=[CH:32][C:31]([CH:34]=[O:35])=[CH:30][N:29]=1.[Cl-].[NH4+]>O1CCCC1>[CH3:26][S:27][C:28]1[N:33]=[CH:32][C:31]([CH:34]([C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)[OH:35])=[CH:30][N:29]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 31518652-(Methylthio)-5-pyrimidinecarbaldehydeHCID 509865195-Iodo-7-(triisopropylsilyl)-7H-pyrrolo-[2,3-d]pyrimidineHCID 178418918HCID 178418918, compound

Product 1

HCID 57963217(2-methylsulfanyl-pyrimidin-5-yl)-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methanolYield 88.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 5-Iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (38, 4.00 g, 9.97 mmol) in 5.00 mL of tetrahydrofuran at −20° C. under nitrogen, isopropylmagnesium chloride (5.80 mL, 2.0 M in tetrahydrofuran, 11.6 mmol) was added slowly. The reaction was allowed to warm to 0° C. over 70 minutes, then cooled to −20° C., followed by addition of 2-methylsulfanyl-pyrimidine-5-carbaldehyde (54, 1.12 g, 7.26 mmol) in 15.0 mL of tetrahydrofuran. The reaction was allowed to warm to room temperature over 1 hour, then poured into aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (55, 2.75 g).

Workup

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

Sources & evidence

ORD record
ord-0755363188374be9bdbe1165f0d9e924
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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