Triethylamine → HCID 58338021, compound

HRID 1409287Notes

Reaction equation

HRID 1409287 reaction equation
ClC1C2N=CSC=2N=CN=1.[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[CH2:20][CH2:21][NH:22][C:23]1[C:24]2[N:31]=[CH:30][S:29][C:25]=2[N:26]=[CH:27][N:28]=1.Cl.FC1C=C(OC)C=CC=1CCN.C(N(CC)CC)C>CN(C=O)C.[Cl-].[NH4+]>[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[CH2:20][CH2:21][NH:22][C:23]1[C:24]2[N:31]=[CH:30][S:29][C:25]=2[N:26]=[CH:27][N:28]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 67031978HCID 67031978, compoundHCID 87349504HCID 87349504, compound

Product 1

HCID 58338021HCID 58338021, compoundYield 22.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

[2-(2-Fluoro-4-methoxyphenyl)-ethyl]-thiazolo[5,4-d]pyrimidin-7-ylamine 7-Chlorothiazolo[5,4-d]pyrimidine (564 mg, 3.3 mmol) was dissolved with magnetic stirring in DMF (10 mL) in a 25 mL round bottom flask equipped with a dry nitrogen line at 25° C. To the solution was added 2-(2-fluoro-4-methoxyphenyl)-ethylamine hydrochloride (700 mg, 3.4 mmol) and triethylamine (Et3N, 1.19 mL, 8.5 mmol). After stirring overnight, the reaction was diluted with saturated (satd) aqueous (aq) ammonium chloride (NH4Cl; 10 mL) and concentrated in vacuo. The residue was partitioned between H2O (10 mL) and EtOAc (3×10 mL). The pooled organic fractions were diluted with pentane (15 mL), washed with H2O (10 mL) and brine (10 mL). After drying (sodium sulfate; Na2SO4), the solution was filtered through a SiO2/cotton plug, and concentrated in vacuo to provide 0.38 g. The aqueous fractions were washed with additional EtOAc, dried (Na2SO4) and filtered through a SiO2/cotton plug, and concentrated in vacuo to provide an additional 0.23 g of crude product. The two fractions were combined and purified by flash column chromatography (SiO2, 0-100% EtOAc/hexane). The appropriate fractions were pooled to afford [2-(2-fluoro-4-methoxyphenyl)-ethyl]-thiazolo[5,4-d]pyrimidin-7-ylamine (Compound 55; 230 mg) as a gold solid: mp 136-139° C.; 1H NMR (DMSO-d6) δ 9.21 (s, 1H), 8.39 (s, 1H), 8.32 (br m, 1H), 7.19 (t, J=8.7 Hz, 1H), 6.77-6.67 (m, 2H), 3.74-3.67 (m, 5H), 2.89 (t, J=7.4 Hz, 3H); ESIMS m/z 305.5 ([M+H]+).

Workup

  1. customequipped with a dry nitrogen line at 25° C
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between H2O (10 mL) and EtOAc (3×10 mL)
  4. additionThe pooled organic fractions were diluted with pentane (15 mL)
  5. washwashed with H2O (10 mL) and brine (10 mL)
  6. dry with materialAfter drying (sodium sulfate; Na2SO4)
  7. filtrationthe solution was filtered through a SiO2/cotton plug
  8. concentrationconcentrated in vacuo
  9. customto provide 0.38 g
  10. washThe aqueous fractions were washed with additional EtOAc
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered through a SiO2/cotton plug
  13. concentrationconcentrated in vacuo
  14. customto provide an additional 0.23 g of crude product
  15. custompurified by flash column chromatography (SiO2, 0-100% EtOAc/hexane)

Sources & evidence

ORD record
ord-0ed35620c316493cae0c2cf69e350370
Source dataset
uspto-grants-2014_12
Patent number
US08921382B2

Reaction notes

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