Ethyl Thioglycolate → [4-(2-tert-Butoxycarbonylaminoethylamino)-5-(4-fluorophenylcarbamoyl)pyrimidin-2-ylsulfanyl]acetic acid ethyl ester

HRID 348493Notes

Reaction equation

HRID 348493 reaction equation
[C:1]([O:5][CH2:6][CH3:7])(=[O:4])[CH2:2][SH:3].[C:8]([O:12][C:13](=[O:38])[NH:14][CH2:15][CH2:16][NH:17][C:18]1[C:23]([C:24](=[O:33])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[CH:22][N:21]=[C:20](S(C)(=O)=O)[N:19]=1)([CH3:11])([CH3:10])[CH3:9].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH2:6]([O:5][C:1](=[O:4])[CH2:2][S:3][C:20]1[N:19]=[C:18]([NH:17][CH2:16][CH2:15][NH:14][C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:38])[C:23]([C:24](=[O:33])[NH:25][C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[CH:22][N:21]=1)[CH3:7]

Participants

6

Reactant 3

HCID 12185Ethyl ThioglycolateHCID 81531DiisopropylethylamineHCID 69523394{2-[5-(4-Fluorophenylcarbamoyl)-2-methylsulfonyl-pyrimidin-4-ylamino]-ethyl}carbamic acid tert-butyl ester

Product 1

HCID 69522205[4-(2-tert-Butoxycarbonylaminoethylamino)-5-(4-fluorophenylcarbamoyl)pyrimidin-2-ylsulfanyl]acetic acid ethyl esterYield 58.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl thioglycolate (73 μL, 0.66 mmol) was added to a solution of {2-[5-(4-fluorophenylcarbamoyl)-2-methylsulfonyl-pyrimidin-4-ylamino]-ethyl}carbamic acid tert-butyl ester (0.30 g, 0.66 mmol) and DIPEA (117 μL, 0.66 mmol) in DMF (1.5 mL). The resulting solution was stirred under N2 overnight. The reaction mixture was then diluted with ethyl acetate (20 mL) and washed with water (10 mL), 1 N HCl (3×10 mL), water (10 mL), saturated NaHCO3 (3×10 mL), water (10 mL), saturated NaCl (20 mL) and dried over MgSO4. Following filtration, the solvent was removed by rotary evaporation to yield the titled product (0.19 g, 58%) as an off-white solid. 1H NMR: (d6-DMSO) δ 10.25 (s, 1H), 8.63 (m, 1H), 8.57 (s, 1H), 7.65 (m, 2H), 7.16 (m, 2H), 6.91 (t, 1H), 4.08 (q, 2H), 3.96 (s, 2H), 3.44 (m, 2H), 3.08 (m, 2H), 1.31 (s, 9H), 1.16 (t, 3H); HPLC: Rt=4.41 min; MS (ESI): m/z 492.44 (M−H)−.

Workup

  1. washwashed with water (10 mL), 1 N HCl (3×10 mL), water (10 mL), saturated NaHCO3 (3×10 mL), water (10 mL), saturated NaCl (20 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltration
  4. customthe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-1cd39bd4c5b0417fbe6b9b2cc0554672
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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