4-Methyl-5-(2-hydroxyethyl)thiazole → HCID 118307685, compound

HRID 718447Notes

Reaction equation

HRID 718447 reaction equation
[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]=[CH:38][S:39][C:40]=1[CH2:41][CH2:42]O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.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][CH2:42][CH2:41][C:40]3[S:39][CH:38]=[N:37][C:36]=3[CH3:35])=[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]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 11364-Methyl-5-(2-hydroxyethyl)thiazoleHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 5462977Diethyl azodicarboxylateHCID 118314205(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307685HCID 118307685, compoundYield 17.39%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

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 (20 mg, 0.043 mmol), 2-(4-methylthiazol-5-yl)ethanol (30.6 mg, 0.213 mmol) and Ph3P-resin (55.8 mg, 0.213 mmol) in THF (2 mL) was added DEAD (0.020 mL, 0.128 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 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-(2-(4-methylthiazol-5-yl)ethoxy)phenyl)pyridin-3-yl)acetic acid (4.2 mg, 7.42 μmol, 17.39% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.87 (s, 1H), 7.39 (d, J=8.4 Hz, 1H), 7.17 (s, 1H), 7.13-7.08 (m, 2H), 5.54 (s, 1H), 4.54-4.41 (m, 6H), 4.26-4.15 (m, 2H), 2.68 (s, 3H), 2.37 (s, 3H), 2.29 (s, 3H), 1.28 (br. s., 4H), 1.15 (s, 9H), 0.80 (br. s., 6H). LCMS (M+H)=566.5.

Workup

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

Sources & evidence

ORD record
ord-9f82c165e54748c6815228ba330bca1e
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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