Methanol → (3R)-3-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid

HRID 526351노트

반응식

HRID 526351 반응식
[C:1]([C:3]1[CH:4]=[C:5]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:6][O:7][C:8]1[CH:9]=[C:10]([C@@H:14]([NH:20][C:21]([C@@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)[CH2:24]2)=[O:22])[CH2:15][C:16]([O:18]C)=[O:17])[CH:11]=[N:12][CH:13]=1)#[N:2].CO.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>C(O)(C)(C)C>[C:1]([C:3]1[CH:4]=[C:5]([CH:46]=[CH:47][C:48]=1[F:49])[CH2:6][O:7][C:8]1[CH:9]=[C:10]([C@H:14]([NH:20][C:21]([C@H:23]2[CH2:28][CH2:27][CH2:26][N:25]([C:29](=[O:45])[CH2:30][CH2:31][CH:32]3[CH2:33][CH2:34][NH:35][CH2:36][CH2:37]3)[CH2:24]2)=[O:22])[CH2:15][C:16]([OH:18])=[O:17])[CH:11]=[N:12][CH:13]=1)#[N:2]

참가 물질

5

반응물 3

HCID 887MethanolHCID 17749109Barium hydroxide, octahydrateHCID 71259840tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate

생성물 1

HCID 71258503(3R)-3-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid수율 14.1%

시약·촉매·용매 1

HCID 6386tert-Butanol용매

실험 절차

Tert-butyl 4-{3-[(3R)-3-{[(1S)-1-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (3.2 mg, 10 μmol) as solved in tert.-butanol (0.15 mL) and methanol (0.13 mL) and barium hydroxide octahydrate (7.4 mg, 20 μmol) was added. After stirring for 45 minutes at room temperature the solvent was distilled off at 0° C. by high vacuum. The residue was solved in water (0.3 mL) and acidified by formic acid (0.9 mL). After 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum and the residue was purified by preparative HPLC to yield 0.8 mg of (3R)-3-{5-[(3-cyano-4-fluorobenzyl)oxy]pyridin-3-yl}-3-[({(3S)-1-[3-(piperidin-4-yl)propanoyl]piperidin-3-yl}carbonyl)amino]propanoic acid.

후처리

  1. distillationwas distilled off at 0° C. by high vacuum
  2. distillationAfter 3 hours at room temperature the solvent was distilled off at 0° C. by high vacuum
  3. customthe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-eac6359dc81f4530b4e62a6e892816b4
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345793B2

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