tert-Butanol → N-[(3S)-1-[6-Chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-N-[[[(1,1-dimethylethoxy)carbonyl]amino]sulfonyl]-glycine, Ethyl Ester

HRID 2217918Notes

Reaction equation

HRID 2217918 reaction equation
[CH3:1][C:2]([OH:5])([CH3:4])[CH3:3].Cl[S:7]([N:10]=[C:11]=[O:12])(=[O:9])=[O:8].[Cl:13][C:14]1[C:15]([C:36]([NH:38][CH2:39][CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)=[O:37])=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([N:24]1[CH2:28][CH2:27][C@H:26]([NH:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:25]1)[CH:18]=[CH:17]2.C(N(CC)CC)C>ClCCl.O>[Cl:13][C:14]1[C:15]([C:36]([NH:38][CH2:39][CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]2)=[O:37])=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[C:19]([N:24]1[CH2:28][CH2:27][C@H:26]([N:29]([S:7]([NH:10][C:11]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:12])(=[O:9])=[O:8])[CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])[CH2:25]1)[CH:18]=[CH:17]2

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 131726984N-[(3S)-1-[6-chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-glycine, Ethyl Ester

Product 1

HCID 131726985N-[(3S)-1-[6-Chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-N-[[[(1,1-dimethylethoxy)carbonyl]amino]sulfonyl]-glycine, Ethyl Ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-methyl-2-propanol (140 mg) in dichloromethane 2 mL) was added over 15 minutes to a stirred solution of chlorosulfonyl isocyanate (0.17 mL) in dichloromethane (16 mL) under nitrogen at 0° C. The mixture was allowed to warm to room temperature over 2 hours and was then added over 20 minutes to a stirred solution of N-[(3S)-1-[6-chloro-5-[[(cyclohexylmethyl)amino]carbonyl]-2-quinolinyl]-3-pyrrolidinyl]-glycine, ethyl ester (Example 112 (a)) (490 mg) and triethylamine (0.25 mL) in dichloromethane (10 mL) under nitrogen at 0° C. After 3 hours, deionised water (10 mL) was added, the layers were separated and the aqueous fraction was extracted with dichloromethane (2×10 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to give an oil. Purification by chromatography (SiO2, dichloromethane:methanol 99:1 as eluant) gave the sub-title compound as a solid (670 mg).

Workup

  1. customthe layers were separated
  2. extractionthe aqueous fraction was extracted with dichloromethane (2×10 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give an oil
  7. customPurification by chromatography (SiO2, dichloromethane:methanol 99:1 as eluant)

Sources & evidence

ORD record
ord-b3dc6ac8a34a496fa553794f61291a36
Source dataset
uspto-grants-2008_08
Patent number
US07408065B2

Reaction notes

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