Hydrochloric Acid → HCID 23508192, compound

HRID 1883600Notes

Reaction equation

HRID 1883600 reaction equation
C([NH:5][C:6]([NH:8][CH:9]([CH2:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1OC)[CH2:10]O)=[S:7])(C)(C)C.[ClH:21].[OH2:22]>>[ClH:21].[NH2:5][C:6]1[S:7][CH2:10][CH:9]([CH2:12][C:13]2[CH:18]=[CH:17][NH:16][C:15](=[O:22])[CH:14]=2)[N:8]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 23508190HCID 23508190, compound

Product 1

HCID 23508192HCID 23508192, compound

Conditions

Temperature
100 °C

Procedure

A suspension of 0.4 g of N-(tert-butyl)-N′-[2-hydroxy-1-(3-methoxy-pyridin-4-yl-methyl)ethyl]-thiourea in 4 mL of aqueous solution of 6N hydrochloric acid is heated at a temperature of about 100° C. for 18 hours. The reaction medium is then concentrated under reduced pressure (2 kPa) at a temperature of about 40° C. The residue obtained is taken up by 25 mL of distilled water and the mixture is washed with 2 times 20 mL of dichloromethane. The aqueous phase is evaporated under reduced pressure (2 kPa) at a temperature of about 40° C. The residue is taken up with 2 times 15 mL of ethanol and concentrated according to the conditions described above, then dried in an oven under reduced pressure (10 kPa) at a temperature of about 40° C. for 4 hours. About 0.31 g of racemic 4-(2-amino-4,5-dihydro-thiazol-4-ylmethyl)-1H-pyridin-2-one hydrochloride, are obtained in the form of a pale yellow solid melting at 124° C. This product is purified by chromatography on a column of CHIRALCEL OD 20μ in an heptane-ethanol-triethylamine mixture (80/20/0.1 by volume). The fractions containing the expected product are collected and concentrated under reduced pressure (1 kPa) at a temperature of about 40° C. and then the residue is dried in an oven under reduced pressure (10 kPa) at a temperature of about 40° C. About 0.0131 g of (+)-4-(2-Hydroxy-pyridin-4-ylmethyl)-4,5-dihydro-thiazol-2-ylamine, (αD2°=+12.1+/−0.7 in the 0.5% DMSO) are obtained. [1H NMR spectrum (300 MHz, (CD3)2SO d6, δ in ppm): 2.73 (dd, J=13.5 and 7 Hz, 1H); 2.80 (dd, J=13.5 and 7 Hz, 1H); 3.27 (dd, J=11.5 and 5.5 Hz, 1H); 3.62 (dd, J=11.5 and 7.5 Hz, 1H); 4.53 (mt, 1H); 6.13 (dd, J=6.5 and 1.5 Hz, 1H); 6.24 (s large, 1H); 7.34 (d, J=6.5Hz, 1H); from 8.90 to 9.40 (mf very broad, 2H); from 9.60 to 10.40 (mf very broad, 1H)].

Workup

  1. concentrationThe reaction medium is then concentrated under reduced pressure (2 kPa) at a temperature of about 40° C
  2. customThe residue obtained
  3. washthe mixture is washed with 2 times 20 mL of dichloromethane
  4. customThe aqueous phase is evaporated under reduced pressure (2 kPa) at a temperature of about 40° C
  5. concentrationconcentrated
  6. customthen dried in an oven under reduced pressure (10 kPa) at a temperature of about 40° C. for 4 hours

Sources & evidence

ORD record
ord-5e141f61ffdc48348e64d0c543011508
Source dataset
uspto-grants-2004_07
Patent number
US06762196B2

Reaction notes

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