Dicyclohexylamine → (5S,8S,10S)-10-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-5-tert-butyl-3,6,12-trioxo-8-(4-pyridin-2-ylbenzyl)-2,11-dioxa-4,7-diazapentadecan-15-oic acid

HRID 1174415ノート

反応式

HRID 1174415 の反応式
[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:14]([NH:16][C@@H:17]([CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@@H:18]([OH:47])[CH2:19][C@@H:20]([NH:34][C:35]([C@@H:37]([NH:42][C:43](=[O:46])[O:44][CH3:45])[C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:24][CH:23]=2)=[O:15])[C:9]1=[O:59])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:60]1(=[O:66])[O:65][C:63](=[O:64])[CH2:62][CH2:61]1.C1(NC2CCCCC2)CCCCC1>O1CCCC1.C(OCC)C>[CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C@@H:13]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:14]([NH:16][C@H:17]([C@@H:18]([O:47][C:60](=[O:66])[CH2:61][CH2:62][C:63]([OH:65])=[O:64])[CH2:19][C@H:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=3)=[CH:24][CH:23]=2)[NH:34][C:35](=[O:36])[C@H:37]([C:38]([CH3:41])([CH3:40])[CH3:39])[NH:42][C:43](=[O:46])[O:44][CH3:45])[CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:15])[C:9]1=[O:59])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 3

HCID 7582DicyclohexylamineHCID 7922Succinic anhydride2 回HCID 11274374A-792611

生成物 1

HCID 11332011(5S,8S,10S)-10-((1S)-1-{[(2S)-2-(3-benzyl-2-oxoimidazolidin-1-yl)-3,3-dimethylbutanoyl]amino}-2-phenylethyl)-5-tert-butyl-3,6,12-trioxo-8-(4-pyridin-2-ylbenzyl)-2,11-dioxa-4,7-diazapentadecan-15-oic acid収率 98.5%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of Example 111 (60 mg, 0.074 mmol) in tetrahydrofuran (0.25 mL) and diethyl ether (0.5 mL) was treated with succinic anhydride (8.2 mg, 0.082 mmol) and dicyclohexylamine (16.3 μL, 0.082 mmol) at 25° C. for 6 h. Over the next 2 days more succinic anhydride (16.4 mg, 0.16 mmol) was added in portions. The mixture was partitioned between dichloromethane and 10% citric acid. The organic layer was separated, washed with brine, dried over MgSO4, and the solvents were evaporated to give the title compound (66 mg, 98%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86(s, 9H), 0.89(s, 9H), 1.25(m, 1H), 1.66(m, 1H), 2.34-2.24(m, 1H), 2.83-2.55(m, 9H), 2.98-2.89(m, 1H), 3.22-2.12(m, 1H), 3.46(s, 3H), 3.86-3.83(d, J=9.93 Hz, 1H), 4.48-1.09(m, 6H), 5.15-5.10(m, 1H), 6.61-6.58(d, J=9.56 Hz, 1H), 7.05-7.00(m, 3H), 7.13-7.11(m, 2H), 7.31-7.25(m, 4H), 7.44-7.36(m, 3H), 7.92-7.87(m, 3H), 7.96(m, 2H), 8.06-8.02(d, J=9.56 Hz, 1H), 8.68-8.66(m, 1H).

後処理

  1. customThe mixture was partitioned between dichloromethane and 10% citric acid
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customthe solvents were evaporated

出典と根拠

ORDレコード
ord-31a6d7c73f3049b0b3b0a311c84ebe1c
出典データセット
uspto-grants-2010_11
特許番号
US07834043B2

反応ノート

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