3-[1-(5-Methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester → 3-[(5-Methyl-thiophen-2-ylmethyl)-(4-spiro[5.5]undec-3-yl-thiazol-2-yl)-amino]-propionic acid tert-butyl ester

HRID 1045066Notes

Reaction equation

HRID 1045066 reaction equation
Br[CH2:2][C:3]([CH:5]1[CH2:10][CH2:9][C:8]2([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[CH2:7][CH2:6]1)=O.[C:16]([O:20][C:21](=[O:35])[CH2:22][CH2:23][N:24]([CH2:28][C:29]1[S:30][C:31]([CH3:34])=[CH:32][CH:33]=1)[C:25]([NH2:27])=[S:26])([CH3:19])([CH3:18])[CH3:17]>CO>[C:16]([O:20][C:21](=[O:35])[CH2:22][CH2:23][N:24]([CH2:28][C:29]1[S:30][C:31]([CH3:34])=[CH:32][CH:33]=1)[C:25]1[S:26][CH:2]=[C:3]([CH:5]2[CH2:10][CH2:9][C:8]3([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3)[CH2:7][CH2:6]2)[N:27]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

4

Reactant 2

HCID 592267123-[1-(5-Methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl esterHCID 866397392-Bromo-1-spiro[5.5]undec-3-yl-ethanone

Product 1

HCID 671802413-[(5-Methyl-thiophen-2-ylmethyl)-(4-spiro[5.5]undec-3-yl-thiazol-2-yl)-amino]-propionic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-bromo-1-spiro[5.5]undec-3-yl-ethanone (200 mg, 0.7 mmol) in MeOH (2 mL) was treated with 3-[1-(5-methyl-thiophen-2-ylmethyl)-thioureido]-propionic acid tert-butyl ester (250 mg, 0.8 mmol) following a method analogous to General Procedure C to produce 3-[(5-methyl-thiophen-2-ylmethyl)-(4-spiro[5.5]undec-3-yl-thiazol-2-yl)-amino]-propionic acid tert-butyl ester after workup and purification (45 mg). This propionate ester derivative (45 mg, 0.09 mmol) was hydrolyzed using NaOH (0.5 mL of 2.0N aq solution in 1 mL of 1:1:MeOH:THF) following a method analogous to General Procedure G1 to produce 3-[(5-methyl-thiophen-2-ylmethyl)-(4-spiro[5.5]undec-3-yl-thiazol-2-yl)-amino]-propionic acid after workup (15 mg, 33% yield). LC-MS m/z: 433 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 6.80 (d, 1H), 6.59 (d, 1H), 6.11 (s, 1H), 4.60 (s, 2H), 3.75 (t, 2H), 2.71 (t, 2H), 2.51 (m, 1H), 2.43 (s, 3H), 1.82 (m, 2H), 1.71 (m, 2H), 1.50 (m, 2H), 1.3-1.5 (m, 7H), 1.27-1.13 (m, 5H). Sodium salt of the title compound could be prepared from the title compound following a method analogous to General Procedure H.

Sources & evidence

ORD record
ord-cf34501291a346fbb413da73cb61ac54
Source dataset
uspto-grants-2013_10
Patent number
US08563742B2

Reaction notes

Loading…