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 526351ノート

反応式

HRID 526351 の反応式
[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]

参加物

5

反応物 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

生成物 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 acid収率 14.1%

試薬・触媒・溶媒 1

HCID 6386tert-Butanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-eac6359dc81f4530b4e62a6e892816b4
出典データセット
uspto-grants-2016_05
特許番号
US09345793B2

反応ノート

読み込み中…