Propylphosphonic anhydride → HCID 89630137, compound

HRID 882151Notes

Reaction equation

HRID 882151 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:22][N:23]([CH3:31])[CH2:24]/[CH:25]=[C:26](\[CH3:30])/[C:27]([O-])=[O:28].[Li+].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCCC1>[CH3:22][N:23]([CH3:31])[CH2:24]/[CH:25]=[C:26](\[CH3:30])/[C:27]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1)=[O:28]

Participants

5

Reactant 3

HCID 111923Propylphosphonic anhydrideHCID 71598790ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylateHCID 131732645HCID 131732645, compound

Product 1

HCID 89630137HCID 89630137, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (100 mg, 0.354 mmol) was added tetrahydrofuran (3.54 mL), TEA (74 μl, 0.53 mmol), lithium (2E)-4-(dimethylamino)-2-methylbut-2-enoate (137 mg, 0.920 mmol) and 1-propanephosphonic acid cyclic anhydride (211 μL, 0.354 mmol). The reaction was stirred at 25° C. overnight and then extracted from aqueous sodium hydrogen carbonate (5%) using ethyl acetate (×3). The organic layers were combined and dried with Na2SO4, filtered, and evaporated in vacuo. The crude product was then taken up in 2 mL of methanol and purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Lyophilization of the desired fractions afforded the title compound as a colorless solid. LRMS (ESI) calc'd for C22H26N5O3 [M+H]+: 408, found 408. 1H NMR (600 MHz, DMSO-D6) 13.06 (bs, 1H), 10.04 (s, 1H), 9.76 (bs, 1H), 8.96 (s, 1H), 8.36 (d, 1H, J=2.8 Hz), 8.08 (s, 1H), 7.85 (dm, 1H, J=9.0 Hz), 7.47 (t, 1H, J=7.8 Hz), 7.36 (dm, 1H, J=7.8 Hz), 6.33 (t, 1H, J=7.2 Hz), 3.98 (apparent t, 1H, J=7.2 Hz), 3.91 (q, 2H, J=7.2 Hz), 2.89 (s, 3H), 2.88 (s, 3H), 2.02 (s, 3H), 0.90 (t, 3H, J=7.2 Hz).

Workup

  1. extractionextracted from aqueous sodium hydrogen carbonate (5%)
  2. dry with materialdried with Na2SO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-1ed1ea6c82ae49f991546e3b7a4448b1
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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