Water → HCID 178460171, compound

HRID 577713Notes

Reaction equation

HRID 577713 reaction equation
[CH3:1][NH:2][C@H:3]1[CH2:6][C@H:5]([O:7][C:8]2[C:9]3[C:23]([C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][NH:21][C:10]=3[N:11]=[C:12]([NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[N:13]=2)[CH2:4]1.O.[C:31](Cl)(=[O:34])[CH:32]=[CH2:33]>C(OCC)(=O)C>[CH3:1][N:2]([C@H:3]1[CH2:6][C@H:5]([O:7][C:8]2[C:9]3[C:23]([C:24]4[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=4)=[CH:22][NH:21][C:10]=3[N:11]=[C:12]([NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[N:13]=2)[CH2:4]1)[C:31](=[O:34])[CH:32]=[CH2:33]

Participants

5

Reactant 3

HCID 962WaterHCID 13140Acryloyl chlorideHCID 178484864HCID 178484864, compound

Product 1

HCID 178460171HCID 178460171, compoundYield 4.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Crude 4-{[trans-3-(methylamino)cyclobutyl]oxy}-N-(1-methyl-1H-pyrazol-4-yl)-5-(pyridin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (0.4 mmol) was partitioned between water (8 mL) and ethyl acetate (15 mL). Acryloyl chloride (36 μL, 0.44 mmol) was added and the mixture stirred at ambient temperature for 1 hr. The organic layer was separated, dried over Na2SO4 and evaporated to give a residue, which was purified by SFC (Zymor Spher Diol Monol, 150×21.2 mm, 5 μm column at 35° C. eluting with a 20%-50% EtOH gradient at 5%/min in CO2 at 140 bar with a flow rate of 60 mL/min) to give the title compound (7.4 mg, 4% yield). 1H NMR (700 MHz, DMSO-17 mm) δ ppm 11.64 (br. s., 1H) 8.87-9.00 (m, 2H) 8.43 (d, J=3.96 Hz, 1H) 8.12 (d, J=7.26 Hz, 1H) 7.87 (br. s., 1H) 7.52 (s, 1H) 7.42 (br. s., 1H) 7.33 (s, 1H) 6.59-6.80 (m, 1H) 5.95-6.15 (m, 1H) 5.65 (br. s., 2H) 5.47 (br. s., 1H) 3.74-3.88 (m, 3H) 3.07 (br. s., 1H) 2.91-3.00 (m, 1H) 2.72 (br. s., 2H) 2.29-2.46 (m, 2H). m/z (APCI+) for C23H24N8O2 445.2 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. customevaporated
  4. customto give a residue, which
  5. customwas purified by SFC (Zymor Spher Diol Monol, 150×21.2 mm, 5 μm column at 35° C.
  6. washeluting with a 20%-50% EtOH gradient at 5%/min in CO2 at 140 bar with a flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-82eafdc0954345b7b11a1844b3bd6fee
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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