Sodium Bicarbonate → [3-((R)-1-{5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylcarbamoyl)-oxetan-3-yl]-carbamic acid 9H-fluoren-9-ylmethyl ester

HRID 1404539ノート

反応式

HRID 1404539 の反応式
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]3([C:23](O)=[O:24])[CH2:22][O:21][CH2:20]3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[Cl:49][C:50]1[CH:51]=[C:52]([F:72])[C:53]([C:66]2[N:70]=[C:69]([CH3:71])[O:68][N:67]=2)=[C:54]([C:56]2[CH:57]=[C:58]([F:65])[C:59]([C@H:62]([NH2:64])[CH3:63])=[N:60][CH:61]=2)[CH:55]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]3([C:23](=[O:24])[NH:64][C@@H:62]([C:59]4[C:58]([F:65])=[CH:57][C:56]([C:54]5[CH:55]=[C:50]([Cl:49])[CH:51]=[C:52]([F:72])[C:53]=5[C:66]5[N:70]=[C:69]([CH3:71])[O:68][N:67]=5)=[CH:61][N:60]=4)[CH3:63])[CH2:22][O:21][CH2:20]3)[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

参加物

8

反応物 5

HCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 679511683-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)oxetane-3-carboxylic acid2 回HCID 68484636(R)-1-{5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylamine

生成物 1

HCID 67979324[3-((R)-1-{5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylcarbamoyl)-oxetan-3-yl]-carbamic acid 9H-fluoren-9-ylmethyl ester

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

実験手順

To a solution of 3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carboxylic acid (77.4 mg, 0.228 mmol, intermediate 8) in dry DMF (2 ml) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (48.1 mg, 0.251 mmol) and 1-hydroxybenzotriazole hydrate (38.4 mg, 0.251 mmol) at room temperature. The resulting colorless solution was stirred for 5 min before a solution of (R)-1-{5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylamine (80.0 mg, 0.228 mmol, step B) in dry DMF (2 ml) was added. This mixture was stirred at room temperature for 1.5 h. Then water was added, the pH was adjusted to 7 with sat. NaHCO3 solution and the mixture was extracted three times with EtOAc. The combined organic layers were washed three times with water and then with brine, dried with Na2SO4 and evaporated. The remaining light brown foam was purified by chromatography (silica gel; DCM/MeOH 98:2-95:5) and the title compound was obtained as off white foam (150 mg, 98%). MS: 672.3 [M+H]+.

後処理

  1. additionwas added
  2. extractionthe mixture was extracted three times with EtOAc
  3. washThe combined organic layers were washed three times with water
  4. dry with materialwith brine, dried with Na2SO4
  5. customevaporated
  6. customThe remaining light brown foam was purified by chromatography (silica gel; DCM/MeOH 98:2-95:5)

出典と根拠

ORDレコード
ord-e48b5611eae447178bf78b1e4474acc8
出典データセット
uspto-grants-2014_12
特許番号
US08912221B2

反応ノート

読み込み中…