Bromotrimethylsilane → (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid

HRID 2407856노트

반응식

HRID 2407856 반응식
[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([O:44][C:45](=[O:57])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:29][O:30][C:31](=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([P:16](=[O:23])([O:20]CC)[O:17]CC)([F:15])[F:14].C[Si](Br)(C)C>C(Cl)Cl>[NH2:1][C@@H:2]([CH2:25][S:26][CH2:27][C@H:28]([O:44][C:45](=[O:57])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:29][O:30][C:31](=[O:43])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])[C:3](=[O:24])[NH:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([P:16](=[O:17])([OH:23])[OH:20])([F:15])[F:14]

참가 물질

4

반응물 2

HCID 76113BromotrimethylsilaneHCID 86678266diethyl (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate

생성물 1

HCID 53476096(12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of diethyl (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonate (1 eq) in DCM (0.1 M) was added trimethylsilyl bromide (10 eq). The reaction mixture was then stirred at room temperature overnight and concentrated. The crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column eluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9) to give (12R,16R)-12-amino-16-(dodecanoyloxy)-1,1-difluoro-11,19-dioxo-4,7,18-trioxa-14-thia-10-azatriacontylphosphonic acid. 1H NMR (CDCl3): δ 8.47 (br s, 1H), 5.10-5.23 (m, 1H), 4.32 (dd, 1H), 4.18-4.26 (m, 1H), 4.12 (dd, 1H), 3.68-3.86 (m, 2H), 3.44-3.68 (m, 6H), 3.20-3.36 (m, 1H), 2.96-3.16 (m, 2H), 2.76-2.85 (m, 1H), 2.68-2.76 (m, 1H), 2.21-2.38 (m, 4H), 2.12-2.07 (m, 2H), 1.52-1.65 (m, 4H), 1.36-1.15 (m, 32H), 0.87 (t, 6H). LRMS [M+H]=805.5.

후처리

  1. concentrationconcentrated
  2. customThe crude mixture was purified by reverse phase high performance liquid chromatography (HPLC) with C4 column
  3. washeluting with a gradient of 40-100% MeCN/10 mM NH4OAc (95:5) in 10 mM NH4OAc (pH 9)

출처 및 근거

ORD 기록
ord-84ca0c7dd982474eb49e1162d18ed26a
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08808703B2

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