4-Methylmorpholine → HCID 66843220、化合物

HRID 254063ノート

反応式

HRID 254063 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([OH:36])=O)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:68][C:69]1[CH:82]=[CH:81][C:72]([CH2:73][S:74][CH2:75][C@H:76]([C:78]([OH:80])=[O:79])[NH2:77])=[CH:71][CH:70]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[OH:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:77][C@@H:76]([C:78]([OH:80])=[O:79])[CH2:75][S:74][CH2:73][C:72]3[CH:81]=[CH:82][C:69]([CH3:68])=[CH:70][CH:71]=3)=[O:36])=[O:31])=[CH:37][CH:38]=2)=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7314856S-4-Methylbenzyl-D-cysteineHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

生成物 1

HCID 66843220HCID 66843220、化合物

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
30 °C

実験手順

To a stirred solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine, (19.9 mg, 0.037 mmol) in DMF (2.0 ml) was added N-methylmorpholine (15 μl, 0.14 mmol). TBTU (14.4 mg, 0.045 mmol) was added and the mixture was stirred at 30° C. for 45 minutes. S-(4-methylbenzyl)-D-cysteine (10.5 mg, 0.047 mmol) was added and the mixture was stirred at 30° C. for 1 hour. The formation of the ketone of the title compound was confirmed. M/z: 748.02 (M+1). Methanol (2 ml) and sodium borohydride (14.7 mg, 0.39 mmol) were added the mixture was stirred for 30 minutes. Ammonium acetate (20 mg) was added and the methanol was removed under reduced pressure. The remaining DMF-solution was purified with preparative HPLC on a C8 column, UV-detection 240/260 nm. A gradient from 20 to 50% MeCN in 0.1M NH4OAc buffer was used as eluent. The pure fractions were collected and the MeCN was removed under reduced pressure. The remaining water solution was acidified to pH 1 with HCl (1M) and extracted with DCM. The combined organic phases were concentrated and the residue was dissolved in MeCN and water. After lyophilisation, the title compound was obtained as a white solid (8.7 mg, 31.5%). H-NMR (400 MHz, DMSO-d6): 2.24 (s, 3H), 2.60-2.68 (m, 1H), 2.72-2.79 (m, 1H), 2.86-2.94 (m, 2H), 3.68 (s, 2H), 3.82 (d, 2H), 4.25 (d, 0.5H), 4.27 (d, 0.5H), 4.39-4.46 (m, 1H), 4.52 (s, 2H), 4.67-4.77 (m, 1H), 5.03 (d, 0.5H), 5.06 (d, 0.5H), 5.60-5.67 (bs, 1H), 6.98 (d, 2H), 7.05-7.18 (m, 8H), 7.20-7.25 (m, 2H), 4.30-4.39 (m, 4H), 8.23-8.32 (m, 2H), 12.80-12.95 (bs, 1H). M/z: 748.04 (M−1).

後処理

  1. stirringthe mixture was stirred at 30° C. for 1 hour

出典と根拠

ORDレコード
ord-f2ba7577a36c4d3e8594049a905d1b09
出典データセット
uspto-grants-2011_01
特許番号
US07871998B2

反応ノート

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