Hydrochloric Acid → 5-(2-chlorobenzylthio)-3-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride

HRID 1426123Notes

Reaction equation

HRID 1426123 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([S:22][CH2:23][CH2:24][C:25](OC)=O)[CH:12]=[N:13][C:14]=1[NH:15][C:16]1[S:17][CH:18]=[C:19]([CH3:21])[N:20]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].BrC[C:37]1[CH:42]=[CH:41]C=C[C:38]=1[Cl:43].[NH4+].[Cl-].Cl>C1COCC1>[ClH:43].[Cl:43][C:38]1[CH:37]=[CH:42][CH:41]=[CH:25][C:24]=1[CH2:23][S:22][C:11]1[CH:10]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:14]([NH:15][C:16]2[S:17][CH:18]=[C:19]([CH3:21])[N:20]=2)=[N:13][CH:12]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11905alpha-Bromo-o-chlorotolueneHCID 25517Ammonium ChlorideHCID 16660505Methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoateHCID 23665647Potassium tert-butoxide

Product 1

HCID 866396725-(2-chlorobenzylthio)-3-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochlorideYield 103.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 1 dram vial was charged with methyl 3-(5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)pyridin-3-ylthio)propanoate (prepared according to Example 42; 70 mg, 0.17 mmol). THF (1 mL) and KOtBu (0.59 mL, 0.59 mmol) were added and the reaction mixture was stirred at room temperature for 5 minutes. 1-(Bromomethyl)-2-chlorobenzene (0.024 mL, 0.19 mmol) was added and the reaction mixture was stirred at room temperature for 30 minutes. Saturated aqueous NH4Cl (1 mL) was added and the reaction mixture was stirred for 10 minutes. The phases were separated and the aqueous phases were washed with EtOAc. The combined organic layers were concentrated and purified on silica gel to afford 5-(2-chlorobenzylthio)-3-(benzyloxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine hydrochloride (48.2 mg, 58.3% yield) as a white solid after HCl salt formation. 1H NMR (d6-DMSO) δ 7.80 (d, 1H), 7.60-7.55 (m, 3H), 7.46-7.34 (m, 4H), 7.27 (td, 1H), 7.18 (td, 1H), 7.10 (dd, 1H), 6.81 (q, 1H), 5.31 (s, 2H), 4.22 (s, 2H), 2.30 (d, 3H); Mass spectrum (apci) m/z=238.0 (100), 454.0 (90), 362.9 (80).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 30 minutes
  2. stirringthe reaction mixture was stirred for 10 minutes
  3. customThe phases were separated
  4. washthe aqueous phases were washed with EtOAc
  5. concentrationThe combined organic layers were concentrated
  6. custompurified on silica gel

Sources & evidence

ORD record
ord-e112bd2ef2f34c40b7b6e19eda1d7cea
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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