Acetic Acid → [6-fluoro-5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)-pyridin-2-yl]-(3,4,5-trimethoxy-benzyl)-amine

HRID 1775186Notes

Reaction equation

HRID 1775186 reaction equation
[F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:18]2[CH:17]=[N:16][CH:15]=[N:14][C:13]=2[NH:12][CH:11]=1.[CH3:19][O:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([O:31][CH3:32])[C:28]=1[O:29][CH3:30])[CH:24]=O.C(O)(=O)C.C([BH3-])#N>C(O)C>[F:1][C:2]1[N:7]=[C:6]([NH:8][CH2:24][C:23]2[CH:26]=[C:27]([O:31][CH3:32])[C:28]([O:29][CH3:30])=[C:21]([O:20][CH3:19])[CH:22]=2)[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:18]2[CH:17]=[N:16][CH:15]=[N:14][C:13]=2[NH:12][CH:11]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 68583,4,5-TrimethoxybenzaldehydeHCID 498716Cyano-borohydrideHCID 579630566-fluoro-5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)-pyridin-2-ylamine

Product 1

HCID 57963135[6-fluoro-5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)-pyridin-2-yl]-(3,4,5-trimethoxy-benzyl)-amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a 2 mL microwave vial, 6-fluoro-5-(7H-pyrrolo[2,3-d]pyrimidin-5-ylmethyl)-pyridin-2-ylamine (68, 9.72 mg, 0.04 mmol) and 3,4,5-trimethoxy-benzaldehyde (69, 15.7 mg, 0.08 mmol) were dissolved in 600 μL of 95:5 ethanol:acetic acid, and silica supported cyanoborohydride (50 mg, 1 mmol/g, 0.05 mmol) was added. The reaction was irradiated for 10 minutes at 160° C. in a microwave. The vial was centrifuged to condense the silica and the supernatant was removed by pipette into another vial. The residual silica was rinsed with 500 μL of ethanol, centrifuged and the supernatant added to the first supernatant. The solvents were removed under vacuum and the resulting material dissolved in dimethyl sulfoxide for purification by HPLC. Samples were purified on Phenomenex C18 column (50 mm×10 mm ID) with mobile phase A of 0.1% trifluoroacetic acid in water, mobile phase B of 0.1% trifluoroacetic acid in acetonitrile, 20-100% B over 16 minutes at a flow rate of 6 mL/min. Appropriate fractions were collected and solvents removed under vacuum to provide the desired compound. MS (ESI) [M+H+]+=424.3.

Workup

  1. additionwas added
  2. customThe reaction was irradiated for 10 minutes at 160° C. in a microwave
  3. customThe vial was centrifuged to condense the silica
  4. customthe supernatant was removed by pipette into another vial
  5. washThe residual silica was rinsed with 500 μL of ethanol
  6. additioncentrifuged and the supernatant added to the first supernatant
  7. customThe solvents were removed under vacuum
  8. dissolutionthe resulting material dissolved in dimethyl sulfoxide for purification by HPLC
  9. customSamples were purified on Phenomenex C18 column (50 mm×10 mm ID) with mobile phase A of 0.1% trifluoroacetic acid in water, mobile phase B of 0.1% trifluoroacetic acid in acetonitrile, 20-100% B over 16 minutes at a flow rate of 6 mL/min
  10. customAppropriate fractions were collected
  11. customsolvents removed under vacuum

Sources & evidence

ORD record
ord-2c8d4833f0ba4f1283e2161d1c5d3baf
Source dataset
uspto-grants-2016_02
Patent number
US09260437B2

Reaction notes

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