Diisopropylethylamine → ethyl 4-{3-[(2-fluoroacryloyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

HRID 882124Notes

Reaction equation

HRID 882124 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.[F:22][C:23](=[CH2:27])[C:24](O)=[O:25].C(OP(ON1C(=O)C2C=CC=CC=2N=N1)(OCC)=O)C.CCN(C(C)C)C(C)C>CC(N(C)C)=O>[F:22][C:23](=[CH2:27])[C:24]([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:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27825232-Fluoroacrylic acidHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 71598790ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 71599414ethyl 4-{3-[(2-fluoroacryloyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (0.028 g, 0.10 mmol), 2-fluoroacrylic acid (0.013 g, 0.15 mmol), 3-[(diethoxyphosphoryl)oxy]-1,2,3-benzotriazin-4(3H)-one (0.060 g, 0.20 mmol), and DIPEA (0.070 mL, 0.40 mmol) were suspended in DMA (1.0 mL) in a sealed tube. The reaction mixture was purged with argon and the reaction flask was capped and heated to 50° C. for 12 hours. The completed reaction was passed through a syringe filter, and was directly purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% NH4OH modifier to afford ethyl 4-{3-[(2-fluoroacryloyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C18H16FN4O3 [M+H]+: 355, found 355. 1H NMR (600 MHz, DMSO-D6) δ 12.99 (s, 1H), 10.44 (s, 1H), 8.91 (s, 1H), 8.32 (s, 1H), 8.09 (t, J=1.8 Hz, 1H), 7.87 (ddd, J=1.1, 2.1, 8.0 Hz, 1H), 7.45 (t, J=7.8 Hz, 1H), 7.40 (dt, J=1.3, 7.7 Hz, 1H), 5.72 (dd, J=3.6, 47.6 Hz, 1H), 5.44 (dd, J=3.7, 15.6 Hz, 1H), 3.85 (q, J=7.1 Hz, 2H), 0.84 (t, J=7.1 Hz, 3H).

Workup

  1. customThe reaction mixture was purged with argon
  2. customthe reaction flask was capped
  3. customThe completed reaction
  4. customwas passed through a syringe
  5. filtrationfilter
  6. customwas directly purified by reverse phase HPLC

Sources & evidence

ORD record
ord-36d4ae81d2f04437be2a8df5e5d7cd5b
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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