Potassium Sodium Tartrate → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenyl]-amide

HRID 601517Notes

Reaction equation

HRID 601517 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH2:26])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([O:15][Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[CH2:11][CH2:10]1.C[Al](C)C.[Cl:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[S:39][C:40]3[C:46](=[O:47])[O:45][CH2:44][CH2:43][C:41]=3[N:42]=2)=[CH:34][CH:33]=1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:26][C:46]([C:40]2[S:39][C:38]([C:35]3[CH:36]=[CH:37][C:32]([Cl:31])=[CH:33][CH:34]=3)=[N:42][C:41]=2[CH2:43][CH2:44][OH:45])=[O:47])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([O:15][Si:16]([CH:20]([CH3:22])[CH3:21])([CH:23]([CH3:25])[CH3:24])[CH:17]([CH3:19])[CH3:18])[CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 16682925TrimethylaluminumHCID 574214852-(4-Chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-oneHCID 575017063-Methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenylamine

Product 1

HCID 575017052-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dissolve the above 3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenylamine (1.41 g, 3.72 mmol) in CH2Cl2 and add a trimethylaluminum solution (2.0M in hexanes, 2.25 mL, 4.50 mmol). Stir the solution at room temperature for 1 h, then add solid 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (1.01 g, 3.80 mmol) and continue stirring at room temperature overnight. Carefully quench reaction with saturated Rochelle's salt solution (15 mL) and stir at room temperature for 1 h. Extract the mixture with CH2Cl2 (3×20 mL). Combine all organic solutions, dry, filter, and concentrate in vacuo. Purify the crude material by flash chromatography using 2N NH3/MeOH in CH2Cl2 as eluent to give the title compound as a sold (1.00 g, 42%). MS (ES+) 644.0 (M+1)+, (ES−) 642.3 (M−1)−. 1H NMR (400 MHz, CDCl3): δ 10.76 (s, 1H), 8.00 (d, 2H, J=8.4 Hz), 7.60 (d, 2H, J=8.8 Hz), 7.35 (d, 1H, J=2.2 Hz), 7.13 (dd, 1H, J=8.8, 2.2 Hz), 6.88 (d, 1H, J=8.8 Hz), 5.78 (t, 1H, J=4.4 Hz), 3.94-3.86 (m, 3H), 3.78 (s, 3H), 3.21-3.13 (m, 4H), 2.78-2.70 (m, 2H), 1.93-1.85 (m, 2H), 1.67-1.57 (m, 2H), 1.06-1.04 (m, 21H).

Workup

  1. stirringcontinue stirring at room temperature overnight
  2. stirringstir at room temperature for 1 h
  3. extractionExtract the mixture with CH2Cl2 (3×20 mL)
  4. customCombine all organic solutions, dry
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-b8803e7344cb47eabcd65ea084f0a305
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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