Hydrochloric Acid → tert-Butyl(S)-1-(2-{4-[5-(trans-2-fluorocyclohexyloxy)-7-propoxyoxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy}acetyl)pyrrolidine-2-carboxylate

HRID 81509Notes

Reaction equation

HRID 81509 reaction equation
[F:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[O:8][C:9]1[N:10]=[C:11]([O:31][CH2:32][CH2:33][CH3:34])[C:12]2[N:17]=[C:16]([C:18]3[CH:28]=[C:27]([CH3:29])[C:21]([O:22][CH2:23][C:24](O)=[O:25])=[C:20]([CH3:30])[CH:19]=3)[O:15][C:13]=2[N:14]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH:66]1[CH2:77][CH2:76][CH2:75][C@H:67]1[C:68]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:69].Cl>O.CN(C)C=O>[F:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[O:8][C:9]1[N:10]=[C:11]([O:31][CH2:32][CH2:33][CH3:34])[C:12]2[N:17]=[C:16]([C:18]3[CH:19]=[C:20]([CH3:30])[C:21]([O:22][CH2:23][C:24]([N:66]4[CH2:77][CH2:76][CH2:75][C@H:67]4[C:68]([O:70][C:71]([CH3:73])([CH3:74])[CH3:72])=[O:69])=[O:25])=[C:27]([CH3:29])[CH:28]=3)[O:15][C:13]=2[N:14]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6453108L-Proline 1,1-dimethylethyl esterHCID 53311354{4-[5-(trans-2-Fluorocyclohexyloxy)-7-propoxyoxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy}acetic acid

Product 1

HCID 86688234tert-Butyl(S)-1-(2-{4-[5-(trans-2-fluorocyclohexyloxy)-7-propoxyoxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy}acetyl)pyrrolidine-2-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

82 mg of {4-[5-(trans-2-fluorocyclohexyloxy)-7-propoxyoxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethylphenoxy}acetic acid were added to 1.5 ml of N,N-dimethylformamide, and 48 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 10 mg of 1-hydroxy-7-azabenzotriazole and 195 μl of N,N-diisopropylethylamine were added, and after 5 min 24 mg of tert-butyl L-prolinate were added. After 16 h at room temperature, 10 ml of water were added, after which the mixture was adjusted to pH 3 by addition of 2 M aqueous hydrochloric acid and extracted twice with ethyl acetate. The combined organic layers were washed with saturated sodium bicarbonate solution and sodium chloride solution, dried and concentrated under reduced pressure. This gave 79 mg of the title compound.

Workup

  1. additionwere added
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic layers were washed with saturated sodium bicarbonate solution and sodium chloride solution
  4. customdried
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6593dee78bc04990adf226ac6474931d
Source dataset
uspto-grants-2014_09
Patent number
US08846691B2

Reaction notes

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