Chloride → HCID 89629990, compound

HRID 882137Notes

Reaction equation

HRID 882137 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]3[C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][NH:15][C:11]=3[N:12]=[CH:13][N:14]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:22]CN(C(C)C)C(C)C.[Cl-].[CH2:32]1C[O:35][CH2:34][CH2:33]1>>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C:9]2[C:10]3[C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][NH:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[CH:3][C:2]=1[NH:1][C:34](=[O:35])[C:33]([CH3:32])=[CH2:22]

Participants

5

Reactant 4

HCID 312ChlorideHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 89630037HCID 89630037, compound

Product 1

HCID 89629990HCID 89629990, compound

Procedure

To a solution of methyl 4-(3-amino-4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (100 mg, 0.349 mmol) and DIPEA (183 μL, 1.05 mmol) in THF (1.7 mL) at room temperature was added methacyloyl chloride (36.5 mg, 0.349 mmol) and the solution was stirred for 1 hour. The desired product 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 2 M aqueous potassium carbonate and the mixture was extracted with ethyl acetate (×5). The combined organic fractions were dried with sodium sulfate, filtered and concentrated under reduced pressure to give methyl 4-{4-fluoro-3-[(2-methylacryloyl)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 13.0 (s, 1H), 9.69 (s, 1H), 8.91 (s, 1H), 8.35 (s, 1H), 7.88 (d, 1H, J=7.04 Hz), 7.42 (m, 1H), 7.35 (t, 1H, J=9.39 Hz), 5.89 (s, 1H), 5.54 (s, 1H), 3.44 (s, 3H), 1.96 (s, 3H).

Workup

  1. customThe desired product was purified by reverse phase HPLC
  2. concentrationThe combined fractions with the desired product were concentrated until only the water layer
  3. extractionthe mixture was extracted with ethyl acetate (×5)
  4. dry with materialThe combined organic fractions were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-548e1c95ba9545b798f1b4de4f37494e
Source dataset
uspto-grants-2015_03
Patent number
US08993756B2

Reaction notes

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