Triethylamine → (S)-1-(2-{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenoxy}-acetyl)-pyrrolidine-2-carboxylic acid

HRID 81363Notes

Reaction equation

HRID 81363 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:24]=[C:23]([CH3:25])[C:17]([O:18][CH2:19][C:20](Cl)=[O:21])=[C:16]([CH3:26])[CH:15]=3)[O:11][C:9]=2[N:10]=1.Cl.C([O:36][C:37](=[O:43])[C@@H:38]1[CH2:42][CH2:41][CH2:40][NH:39]1)(C)(C)C.C(N(CC)CC)C>ClCCl>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]2[N:13]=[C:12]([C:14]3[CH:24]=[C:23]([CH3:25])[C:17]([O:18][CH2:19][C:20]([N:39]4[CH2:40][CH2:41][CH2:42][C@H:38]4[C:37]([OH:43])=[O:36])=[O:21])=[C:16]([CH3:26])[CH:15]=3)[O:11][C:9]=2[N:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 6453107tert-Butyl L-prolinate hydrochlorideHCID 86679069{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenoxy}-acetyl chloride

Product 1

HCID 53262540(S)-1-(2-{4-[5-(2-Fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenoxy}-acetyl)-pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 175 mg of {4-[5-(2-fluoro-phenoxy)-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenoxy}-acetyl chloride in 2 ml of dichloromethane was added slowly to a suspension of 102 mg of proline tert-butyl ester hydrochloride and 170 μl of triethylamine in 5 ml of dichloromethane. After stirring for 2 h, the solvent was removed in vacuo. 1.6 ml of trifluoroacetic acid were added and the mixture was stirred for 2 h at room temperature. Then 10 ml water were added and the aqueous layer was extracted three times with 15 ml of a dichloromethane/isopropanol mixture (3:1). After drying with sodium sulfate and filtration, the solvents were removed in vacuo and the title compound was isolated via preparative HPLC. Yield: 56 mg of a white solid.

Workup

  1. customthe solvent was removed in vacuo
  2. addition1.6 ml of trifluoroacetic acid were added
  3. stirringthe mixture was stirred for 2 h at room temperature
  4. additionThen 10 ml water were added
  5. extractionthe aqueous layer was extracted three times with 15 ml of a dichloromethane/isopropanol mixture (3:1)
  6. dry with materialAfter drying with sodium sulfate and filtration
  7. customthe solvents were removed in vacuo

Sources & evidence

ORD record
ord-779f5e41cd7c4b9d99e8da88af257a4f
Source dataset
uspto-grants-2014_09
Patent number
US08846690B2

Reaction notes

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