Hydrochloric Acid → (S)-1-((E)-3-{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-phenyl}-acryloyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 81366Notes

Reaction equation

HRID 81366 reaction equation
[F:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22](O)=[O:23])=[CH:16][CH:15]=3)[O:11][C:9]=2[N:10]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[C:60]([O:64][C:65](=[O:71])[C@@H:66]1[CH2:70][CH2:69][CH2:68][NH:67]1)([CH3:63])([CH3:62])[CH3:61].Cl>CN(C)C=O.O>[C:60]([O:64][C:65]([C@@H:66]1[CH2:70][CH2:69][CH2:68][N:67]1[C:22](=[O:23])/[CH:21]=[CH:20]/[C:17]1[CH:18]=[CH:19][C:14]([C:12]2[O:11][C:9]3[N:10]=[C:5]([O:4][C:3]4[CH:25]=[CH:26][CH:27]=[CH:28][C:2]=4[F:1])[N:6]=[CH:7][C:8]=3[N:13]=2)=[CH:15][CH:16]=1)=[O:71])([CH3:63])([CH3:61])[CH3:62]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6453108L-Proline 1,1-dimethylethyl esterHCID 53312044(E)-3-{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-phenyl}-acrylic acid

Product 1

HCID 86679072(S)-1-((E)-3-{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-phenyl}-acryloyl)-pyrrolidine-2-carboxylic acid tert-butyl esterYield 39.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

140 mg of {(E)-3-{4-[5-(2-fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-phenyl}-acrylic acid were dissolved in 2 ml of N,N-dimethylformamide, and 98 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 19 mg of 1-hydroxy-7-azabenzotriazole and 397 μl of N,N-diisopropylethylamine were added, followed by the addition of 49 mg of L-proline tert-butyl ester after 5 min. After 16 h at room temperature, 10 ml of water were added, and the mixture was brought to pH 3 by addition of 2 M aqueous hydrochloric acid and extracted twice with ethyl acetate. The combined organic layers were washed with a saturated sodium hydrogencarbonate solution and brine, dried and concentrated in vacuo. The residue was purified by preparative HPLC. 60 mg of the title compound were obtained.

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic layers were washed with a saturated sodium hydrogencarbonate solution and brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-18d82c7de99541f6ace7be117398ce1e
Source dataset
uspto-grants-2014_09
Patent number
US08846690B2

Reaction notes

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