Trifluoroacetic acid → HCID 178460284, compound

HRID 577685Notes

Reaction equation

HRID 577685 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]2[N:9]=[C:10]([NH:25][C@H:26]3[CH2:29][C@H:28]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])[CH2:27]3)[C:11]3[CH:16]=[CH:15][N:14]([CH2:17][O:18]CC[Si](C)(C)C)[C:12]=3[N:13]=2)[CH:4]=[N:3]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:18][CH2:17][N:14]1[C:12]2[N:13]=[C:8]([NH:7][C:5]3[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=3)[N:9]=[C:10]([NH:25][C@H:26]3[CH2:29][C@H:28]([NH:30][C:31](=[O:34])[CH:32]=[CH2:33])[CH2:27]3)[C:11]=2[CH:16]=[CH:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 178460285HCID 178460285, compound

Product 1

HCID 178460284HCID 178460284, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-{trans-3-[(2-[(1-methyl-1H-pyrazol-4-yl)amino]-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}prop-2-enamide (18 mmol) was dissolved in DCM (5 mL) and TFA (0.5 mL) was added. After stirring for 3 hrs, the solvents were removed and chromatography eluting with a gradient of 2%-20% EtOH in DCM to afford N-[trans-3-({7-(hydroxymethyl)-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)cyclobutyl]prop-2-enamide. To this N-hydroxymethyl intermediate, was added EtOH (5 mL) and K2CO3 (100 mg) dissolved in water (2.5 mL). The reaction was allowed to stir for 6 hrs and the solvents were removed. Water (3 mL) was added and the product was extracted into 2-methyl-THF (four×3 mL). After drying the organic extract over MgSO4, filtering, and concentrating, the white residue was carefully precipitated from DCM/MeOH/heptane (1:1:1) to afford the title compound (16 mg, 26% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.8 (br. s., 1H), 8.52 (d, J=6.80 Hz, 1H), 8.32 (s, 1H), 7.86 (s, 1H), 7.45 (s, 1H), 6.87 (s, 1H), 6.72 (br. s., 1H), 6.64 (s, 1H), 6.18-6.29 (m, 1H), 6.12 (d, J=1.76 Hz, 1H), 5.60 (dd, J=10.07, 2.01 Hz, 1H), 4.68 (d, J=6.29 Hz, 1H), 4.40 (d, J=6.55 Hz, 1H), 2.37 (br. s., 3H), 2.18 (s, 2H). m/z (APCI+) for C17H20N8O 353.1 (M+H)+.

Workup

  1. customthe solvents were removed
  2. washchromatography eluting with a gradient of 2%-20% EtOH in DCM

Sources & evidence

ORD record
ord-bd9f4107a9b945d5b987cd5441973410
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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