Trifluoroacetic acid → HCID 86681008, compound

HRID 1847970Notes

Reaction equation

HRID 1847970 reaction equation
CO[CH:3]([C:21]1[C:29]2[C:24](=[N:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1)[C:4]1[CH:20]=[CH:19][C:7]2[N:8]=[C:9]([NH:11][C@@H:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]3[OH:18])[S:10][C:6]=2[CH:5]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>CC#N>[NH:23]1[C:24]2=[N:25][CH:26]=[CH:27][CH:28]=[C:29]2[C:21]([CH2:3][C:4]2[CH:20]=[CH:19][C:7]3[N:8]=[C:9]([NH:11][C@@H:12]4[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]4[OH:18])[S:10][C:6]=3[CH:5]=2)=[CH:22]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86681007HCID 86681007, compound

Product 1

HCID 86681008HCID 86681008, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (1R,2R)-2-((6-(methoxy(1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (20 mg, 0.049 mmol) from Step 3 of Example 12 in CH3CN (10 mL) were added triethylsilane (11.4 mg, 0.092 mmol) and TFA (10.4 mg, 0.092 mmol) at rt. The mixture was stirred at 60° C. overnight. After cooling to rt, the reaction mixture was concentrated under reduced pressure. The crude product was purified by HPLC using a mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (5.7 mg, 31%) as a brown solid. 1H NMR (300 MHz, DMSO-d6) δ 11.71 (br s, 1H), 9.56 (br s, 1H), 8.23 (d, J=4.1 Hz, 1H), 7.93 (d, J=7.0 Hz, 1H), 7.70 (s, 1H), 7.26-7.42 (m, 3H), 7.07 (dd, J=4.9, 7.9 Hz, 1H), 4.11 (s, 2H), 3.53 (br s, 1H), 3.27-3.43 (m, 2H), 1.83-2.12 (m, 2H), 1.66 (br s, 2H), 1.27 (br s, 4H). LCMS (ESI) m/z 379 (M+H)+.

Workup

  1. temperatureAfter cooling to rt
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customThe crude product was purified by HPLC
  4. additiona mixture of water (5% CH3CN, 0.05% AcOH) and CH3CN (0.05% AcOH) as the mobile phase and Varian Pursuit XRs Diphenyl column as the stationary phase

Sources & evidence

ORD record
ord-07c647e601de4277a3d3af53ca9de2e8
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

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