Sodium Bicarbonate → {5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-6-methyl-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester

HRID 1403288Notes

Reaction equation

HRID 1403288 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.[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]=[O:49])=[C:44]([CH3:50])[N:43]=1)[CH2:33][C:34]1[CH:35]=[N:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)([CH3:29])([CH3:28])[CH3:27].C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]([OH:49])[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)=[C:44]([CH3:50])[N:43]=1)[CH2:33][C:34]1[CH:35]=[N:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)([CH3:29])([CH3:28])[CH3:27]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 509865195-Iodo-7-(triisopropylsilyl)-7H-pyrrolo-[2,3-d]pyrimidineHCID 57963057(5-Formyl-6-methyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl esterHCID 178418918HCID 178418918, compound

Product 1

HCID 57963213{5-[hydroxy-(7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-methyl]-6-methyl-pyridin-2-yl}-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl esterYield 59.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-25 °C

Procedure

To 5-iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (38, 0.37 g, 0.92 mmol) in a round bottom flask, 1.1 mL of tetrahydrofuran was added and the mixture cooled to −25° C. Isopropylmagnesium chloride (0.49 mL, 2.0 M in tetrahydrofuran, 0.97 mmol) was added and the reaction stirred, coming to 0° C. The reaction was cooled to −25° C. and (5-formyl-6-methyl-pyridin-2-yl)-(6-methoxy-pyridin-3-ylmethyl)-carbamic acid tert-butyl ester (74, 0.300 g, 0.839 mmol) in 2.5 mL of tetrahydrofuran was added. The reaction was stirred, coming to 0° C., then poured into aqueous saturated sodium bicarbonate and ethyl acetate. The organic layer was washed with brine, then dried over sodium sulfate, filtered and the filtrate adsorbed onto silica. This was purified by silica gel column chromatography eluting with 10-80% ethyl acetate in hexanes. Appropriate fractions were combined and the solvents removed under vacuum to provide the desired compound (75, 317 mg). MS (ESI) [M+H+]+=634.09.

Workup

  1. customcoming to 0° C
  2. temperatureThe reaction was cooled to −25° C.
  3. stirringThe reaction was stirred
  4. customcoming to 0° C.
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customThis was purified by silica gel column chromatography
  9. washeluting with 10-80% ethyl acetate in hexanes
  10. customthe solvents removed under vacuum

Sources & evidence

ORD record
ord-091a3841b0014190a037fd00d18f806b
Source dataset
uspto-grants-2014_12
Patent number
US08912204B2

Reaction notes

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