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

HRID 525505Notes

Reaction equation

HRID 525505 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 (1604, 1.15 mmol) followed by methanesulfonyl chloride (304, 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-ce11055f40224853b55f49184d63f67f
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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