Sodium Hydroxide → (2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-5-[4-[(4-methyl-2-phenyl-thiazol-5-yl)methoxy]phenyl]-3-pyridyl]acetic acid

HRID 718451

반응식

HRID 718451 반응식
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:35][C:36]1[N:37]=[C:38]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[S:39][C:40]=1[CH2:41]O.CCOC(/N=N/C(OCC)=O)=O.[OH-].[Na+]>C1COCC1.CO>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:34])=[N:14][C:15]([CH3:33])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:41][C:40]3[S:39][C:38]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)=[N:37][C:36]=3[CH3:35])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:24])([CH3:25])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:3])([CH3:2])[CH3:4]

참가 물질

7

반응물 4

HCID 14798Sodium HydroxideHCID 736541(4-Methyl-2-phenyl-thiazol-5-yl)-methanolHCID 5462977Diethyl azodicarboxylateHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

생성물 1

HCID 118307815(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-5-[4-[(4-methyl-2-phenyl-thiazol-5-yl)methoxy]phenyl]-3-pyridyl]acetic acid수율 34.6%

시약·촉매·용매 2

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

실험 절차

To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (25 mg, 0.053 mmol), (4-methyl-2-phenylthiazol-5-yl)methanol (32.9 mg, 0.160 mmol) and Ph3-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DEAD (0.025 mL, 0.160 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (1.067 mL, 1.067 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-((4-methyl-2-phenylthiazol-5-yl)methoxy)phenyl)pyridin-3-yl)acetic acid (11.6 mg, 0.018 mmol, 34.6% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.89 (d, J=7.3 Hz, 2H), 7.52-7.41 (m, 4H), 7.25 (d, J=8.1 Hz, 1H), 7.14 (t, J=7.9 Hz, 2H), 7.10-7.04 (m, 1H), 5.82 (br. s., 1H), 5.41 (q, J=12.8 Hz, 2H), 3.26 (d, J=11.7 Hz, 1H), 2.77 (br. s., 1H), 2.47 (s, 3H), 2.43 (s, 3H), 2.15 (d, J=10.3 Hz, 1H), 2.07 (s, 3H), 1.88 (br. s., 1H), 1.46 (br. s., 1H), 1.24 (br. s., 1H), 1.15 (br. s., 1H), 1.12 (s, 9H), 0.92 (d, J=10.3 Hz, 1H), 0.77 (br. s., 3H), 0.51 (br. s., 3H). LCMS (M+H)=628.6.

후처리

  1. filtrationmixture was filtered
  2. customto remove polymer
  3. concentrationconcentrated
  4. temperatureMixture was then cooled
  5. custompurified by prep-HPLC

출처 및 근거

ORD 기록
ord-2245934141eb47fe8e24213d3e3d7674
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193720B2

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