Acetonitrile → HCID 89616010, compound

HRID 882118Notes

Reaction equation

HRID 882118 reaction equation
[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([C:11]3[C:12]4[C:19]([C:20]([O:22][CH2:23][CH:24]=[CH2:25])=[O:21])=[CH:18][N:17](COCC[Si](C)(C)C)[C:13]=4[N:14]=[CH:15][N:16]=3)[CH:7]=[CH:8]2)=[N:3]1.C(O)(C(F)(F)F)=O.C(#N)C.[OH-].[NH4+]>C(Cl)Cl>[CH3:1][N:2]1[CH:10]=[C:9]2[C:4]([CH:5]=[C:6]([C:11]3[C:12]4[C:19]([C:20]([O:22][CH2:23][CH:24]=[CH2:25])=[O:21])=[CH:18][NH:17][C:13]=4[N:14]=[CH:15][N:16]=3)[CH:7]=[CH:8]2)=[N:3]1

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 6422Trifluoroacetic acidHCID 14923Ammonium HydroxideHCID 89630017HCID 89630017, compound

Product 1

HCID 89616010HCID 89616010, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prop-2-en-1-yl 4-(2-methyl-2H-indazol-6-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate was dissolved in DCM (1.0 mL) and then TFA (0.91 mL, 12 mmol) was added. The resulting solution was stirred for 2 hours at room temperature before being concentrated in vacuo. Acetonitrile (0.50 mL) and ammonium hydroxide (0.50 mL, 3.6 mmol) were added to the residue and the solution was heated to 50° C. for 3 hours. The reaction was concentrated in vacuo and purified by reverse phase chromatography using a 5-35% acetonitrile gradient in water with 0.1% TFA modifier. Pure fractions were free-based by extracting from a saturated sodium bicarbonate solution using 3:1 CHCl3:IPA (×3). The combined organic layers were then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford prop-2-en-1-yl 4-(2-methyl-2H-indazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate as a white solid. LRMS (ESI) calcd for C18H16N5O2 [M+H]+: 334, found 334. 1H NMR (600 MHz, DMSO-D6) δ 13.04 (s, 1H), 8.96 (s, 1H), 8.43 (s, 1H), 8.39 (s, 1H), 7.81 (m, 1H), 7.79 (dd, 1H, J=8.4, 0.8 Hz), 7.39 (dd, 1H, J=8.4, 1.4 Hz), 5.5 (m, 1H), 4.97-5.04 (m, 2H), 4.30 (dm, 2H, J=5.7 Hz), 4.25 (s, 3H).

Workup

  1. concentrationbefore being concentrated in vacuo
  2. temperaturethe solution was heated to 50° C. for 3 hours
  3. concentrationThe reaction was concentrated in vacuo
  4. custompurified by reverse phase chromatography
  5. extractionby extracting from a saturated sodium bicarbonate solution
  6. washThe combined organic layers were then washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-76a57905b1bc407f8d2d215852b8adb8
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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