Dimethylamine → HCID 89630042, compound

HRID 882147Notes

Reaction equation

HRID 882147 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.Br[CH2:23]/[CH:24]=[CH:25]/[C:26](Br)=[O:27].[CH3:29][NH:30][CH3:31].O>C1COCC1>[CH2:20]([O:19][C:17]([C:16]1[C:9]2[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:26](=[O:27])/[CH:25]=[CH:24]/[CH2:23][N:30]([CH3:31])[CH3:29])[CH:3]=3)=[N:13][CH:12]=[N:11][C:10]=2[NH:14][CH:15]=1)=[O:18])[CH3:21]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 962WaterHCID 59587031HCID 59587031, compoundHCID 71598790ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate

Product 1

HCID 89630042HCID 89630042, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (100 mg, 0.354 mmol) in THF (2 mL) was added (E)-4-bromobut-2-enoyl bromide (0.400 mmol) and the resulting reaction mixture was stirred for 1 hour at 0° C. Dimethylamine (0.886 mL, 1.77 mmol, 2 M in THF) was then added and the reaction mixture was sealed and stirred overnight. Water (10 mL) was added and the mixture was extracted with ethyl acetate (×3). The combined organic fractions were dried over sodium sulfate, filtered and concentrated under reduced pressure. The reaction was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. The combined fractions with the desired product were concentrated until only the water layer remained. The water layer was neutralized with saturated aqueous sodium bicarbonate and the mixture was extracted with ethyl acetate (×5). The combined organic fractions were dried over sodium sulfate, filtered and concentrated under reduced pressure to give ethyl-4-(3-{[(2E)-4-(dimethylamino)but-2-enoyl]amino}phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C21H24N5O3 [M+H]+: 394, found 394. 1H NMR (600 MHz, DMSO-D6) δ 13.0 (s, 1H), 10.2 (s, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 8.00 (s, 1H), 7.78 (d, 1H, J=8.21 Hz), 7.41 (t, 1H, J=8.21 Hz), 7.31 (d, 1H, J=7.63 Hz), 6.73 (dt, 1H, J=15.3, 5.87 Hz), 6.27 (d, 1H, J=15.3 Hz), 3.84 (q, 2H, J=7.04 Hz), 3.06 (d, 2H, J=5.87 Hz), 2.18 (s, 6H), 0.83 (t, 3H, J=7.04 Hz).

Workup

  1. customthe resulting reaction mixture
  2. customthe reaction mixture was sealed
  3. stirringstirred overnight
  4. extractionthe mixture was extracted with ethyl acetate (×3)
  5. dry with materialThe combined organic fractions were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe reaction was purified by reverse phase HPLC
  9. concentrationThe combined fractions with the desired product were concentrated until only the water layer
  10. extractionthe mixture was extracted with ethyl acetate (×5)
  11. dry with materialThe combined organic fractions were dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-76d9cbbbe65c4419b2fee26f89c2af52
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

Loading…