Triethylamine → 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(5-(methylsulfonamidomethyl)thiophen-2-yl)phenyl)propan-2-yl)acetamide

HRID 1520436Notes

Reaction equation

HRID 1520436 reaction equation
[NH2:1][CH2:2][C:3]1[S:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]([OH:24])[C@H:15]([NH:18][C:19](=[O:23])[CH:20]([Cl:22])[Cl:21])[CH2:16][F:17])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>ClCCl>[Cl:21][CH:20]([Cl:22])[C:19]([NH:18][C@H:15]([CH2:16][F:17])[C@H:14]([OH:24])[C:11]1[CH:10]=[CH:9][C:8]([C:6]2[S:7][C:3]([CH2:2][NH:1][S:33]([CH3:32])(=[O:35])=[O:34])=[CH:4][CH:5]=2)=[CH:13][CH:12]=1)=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86695384N-((1R,2S)-1-(4-(5-(aminomethyl)thiophen-2-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamide

Product 1

HCID 866953852,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(5-(methylsulfonamidomethyl)thiophen-2-yl)phenyl)propan-2-yl)acetamideYield 55.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of N-((1R,2S)-1-(4-(5-(aminomethyl)thiophen-2-yl)phenyl)-3-fluoro-1-hydroxypropan-2-yl)-2,2-dichloroacetamide (150 mg, 0.383 mmol) in dichloromethane is added triethylamine (160 μL, 1.15 mmol) followed by methanesulfonyl chloride (30 μL, 0.383 mmol). Resulting yellow solution is stirred at room temperature for 30 minutes. The reaction is concentrated then purified using HPLC to give the title compound (99 mg): 1HNMR (400 MHz, DMSO-d6): δ 8.58 (d, 1H), 7.71 (t, 1H), 7.55 (d, 2H), 7.37 (d, 2H), 7.33 (d, 2H), 7.01 (d, 1H), 6.51 (s, 1H), 5.95 (br s, 1H), 4.85 (d, 1H), 4.71-4.52 (m, 1H), 4.44-4.13 (m, 4H), 2.89 (s, 3H).

Workup

  1. customResulting yellow solution
  2. concentrationThe reaction is concentrated
  3. customthen purified

Sources & evidence

ORD record
ord-05897529adf24494bead773efa321f36
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

Loading…