Trifluoroacetic acid → HCID 178507870, compound

HRID 1529457Notes

Reaction equation

HRID 1529457 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]2[C:14]([C:27]3[N:32]=[C:31](S(C)(=O)=O)[N:30]=[C:29]([N:37]4[CH2:42][CH2:41][CH:40]([NH:43]C(=O)OC(C)(C)C)[CH2:39][CH2:38]4)[CH:28]=3)=[CH:15][N:16](S(C3C=CC(C)=CC=3)(=O)=O)[C:11]2=[CH:10][CH:9]=1.[OH-].[Na+].C(O)(C(F)(F)F)=[O:54]>O1CCOCC1.C(Cl)(Cl)Cl.CC(O)C>[NH2:43][CH:40]1[CH2:39][CH2:38][N:37]([C:29]2[CH:28]=[C:27]([C:14]3[C:12]4=[N:13][C:8]([C:3]5[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=5[F:1])=[CH:9][CH:10]=[C:11]4[NH:16][CH:15]=3)[N:32]=[C:31]([OH:54])[N:30]=2)[CH2:42][CH2:41]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 67959655tert-butyl 1-(6-(5-(2-fluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl)piperidin-4-ylcarbamate

Product 1

HCID 178507870HCID 178507870, compoundYield 64.2%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with tert-butyl 1-(6-(5-(2-fluorophenyl)-1-tosyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl)piperidin-4-ylcarbamate (100 mg, 0.139 mmol) and NaOH (0.3 mL, 0.600 mmol) in p-dioxane (2 mL). The reaction was stirred and heated in a Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden) at 100° C. for 1 h. The mixture was diluted with CHCl3/iPrOH (4:1) and washed with water. The organic layer was dried, filtered and concentrated. The residue was dissolved in DCM (1 mL) and TFA (200 μL, 2.60 mmol) was added. The reaction was stirred at RT for 15 min, then the solvent was removed. The residue was purified with preparative HPLC (eluting with 5-30% ACN in water in 30 min) to give 4-(4-aminopiperidin-1-yl)-6-(5-(2-fluorophenyl)-1H-pyrrolo[3,2-b]pyridin-3-yl)pyrimidin-2-ol (36.0 mg, 0.089 mmol, 64.2% yield) as a TFA salt. MS (ESI, pos. ion) m/z: 405.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 12.51 (1 H, br. s.), 8.79 (1 H, d, J=3.1 Hz), 8.12 (1 H, d, J=8.6 Hz), 7.85-8.05 (4 H, m), 7.76 (1 H, dd, J=8.5, 1.9 Hz), 7.46-7.61 (2 H, m), 7.32-7.44 (2 H, m), 4.19-4.55 (2 H, m), 3.37-3.52 (2 H, m), 3.10-3.33 (2 H, m), 2.04 (2 H, d, J=11.2 Hz), 1.47-1.68 (2 H, m).

Workup

  1. customA glass microwave reaction vessel
  2. washwashed with water
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in DCM (1 mL)
  7. stirringThe reaction was stirred at RT for 15 min
  8. customthe solvent was removed
  9. customThe residue was purified with preparative HPLC (eluting with 5-30% ACN in water in 30 min)

Sources & evidence

ORD record
ord-3ac9ff3dfe3f4170929c3b9e70c7704f
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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