Sodium Iodide → HCID 58710016, compound

HRID 2375865Notes

Reaction equation

HRID 2375865 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[NH:31][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:22][C:23]4[CH:24]=[N:25][C:26]([O:29]C)=[CH:27][CH:28]=4)[C:16]=3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Na+].[I-].C[Si](Cl)(C)C.C([O-])(O)=O.[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>CC#N.CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]=[C:11]([C:14]2[NH:31][C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH:22][C:23]4[CH:28]=[CH:27][C:26](=[O:29])[NH:25][CH:24]=4)[C:16]=3[CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 58709883HCID 58709883, compound

Product 1

HCID 58710016HCID 58710016, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Into the suspension of 4-[4-(6-methoxypyridin-3-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (68.4 mg, 79% purity, 0.127 mmol) and NaI (19.1 mg, 0.127 mmol) in CH3CN (10 mL) was added trimethylsilyl chloride (1 M in THF, 0.765 mL, 0.765 mmol) at rt. The mixture was then heated at 80° C. in a flask under N2 for 48 h. After that time, the mixture was cooled at 0° C. and the aqueous solution (H2O, 8 mL) of NaHCO3 (159 mg) and NaS2O4.5H2O (318 mg) was added while stirring. The solid was filtered off and washed with water to obtain a brown-red solid. Boc2O (30.8 mg, 0.140 mmol), DMAP (17.1 mg, 0.140 mmol) and the above solid were dissolved in pyridine and the mixture was stirred at rt for 18 h. After that time, the mixture was concentrated in vacuo to obtain a green-yellow oil that was submitted for MS directed purification. One obtained the title compound as off-white solid. 1H NMR (DMSO-d6, 400 MHz): δ=1.44 (s, 9H), 2.46 (brs, 2H), 3.56 (t, 2H, J=5.4 Hz), 4.00 (brs, 2H), 6.38 (s, 1H), 6.40 (s, 1H), 6.67-7.70 (m, 1H), 8.02 (d, 1H, J=2.4 Hz), 8.20 (s, 1H), 9.06 (s, 1H), 11.40 (brs, 1H), 11.92 (s 1H). MS (ES+): m/z 409.05 (100) [MH+]. HPLC: tR=2.33 min (ZQ2000, polar—5 min).

Workup

  1. temperatureAfter that time, the mixture was cooled at 0° C.
  2. filtrationThe solid was filtered off
  3. washwashed with water
  4. customto obtain a brown-red solid
  5. stirringthe mixture was stirred at rt for 18 h
  6. concentrationAfter that time, the mixture was concentrated in vacuo
  7. customto obtain a green-yellow oil that
  8. custompurification

Sources & evidence

ORD record
ord-5a0e9fb04cde4c03b9c54703012ef69a
Source dataset
uspto-grants-2008_12
Patent number
US07465726B2

Reaction notes

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