Trifluoroacetic acid → HCID 86670410, compound

HRID 1972620Notes

Reaction equation

HRID 1972620 reaction equation
[CH3:1][S:2]([N:5]([CH2:12][C@@H:13]1[N:18]([C:19]2[N:24]=[CH:23][C:22]([C:25]([OH:34])([C:30]([F:33])([F:32])[F:31])[C:26]([F:29])([F:28])[F:27])=[CH:21][N:20]=2)[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:4])=[O:3].C(O)(C(F)(F)F)=O.C(N(CC)CC)C.[Cl:56][C:57]1[N:62]=[CH:61][C:60]([S:63](Cl)(=[O:65])=[O:64])=[CH:59][CH:58]=1>C(Cl)Cl>[Cl:56][C:57]1[N:62]=[CH:61][C:60]([S:63]([N:15]2[CH2:16][CH2:17][N:18]([C:19]3[N:20]=[CH:21][C:22]([C:25]([OH:34])([C:26]([F:28])([F:29])[F:27])[C:30]([F:33])([F:31])[F:32])=[CH:23][N:24]=3)[C@@H:13]([CH2:12][N:5]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[S:2]([CH3:1])(=[O:4])=[O:3])[CH2:14]2)(=[O:65])=[O:64])=[CH:59][CH:58]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 27927922-Chloro-5-pyridinesulfonyl chlorideHCID 86670407HCID 86670407, compound

Product 1

HCID 86670410HCID 86670410, compoundYield 55.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 5-mL vial was charged with (R)-tert-butyl 4-(5-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)pyrimidin-2-yl)-3-((N-phenylmethylsulfonamido)methyl)piperazine-1-carboxylate (0.214 g, 0.348 mmol, Example 233, Step 5), TFA (1.0 mL, 13 mmol) and CH2Cl2 (2 mL). The mixture was stirred at room temperature for 35 min and then concentrated. CH2Cl2 (2 mL) and triethylamine (0.50 mL, 3.6 mmol) were added and the mixture was stirred at room temperature for 10 min. 6-chloropyridine-3-sulfonyl chloride (0.0910 g, 0.429 mmol, Organic Process Research & Development 2009, 13, 875) was then added in potions and the mixture was stirred at room temperature for 1.5 h. The mixture was concentrated and purified by column chromatography (50 g of silica gel, 0 to 60% EtOAc in hexanes) to afford N-(((2R)-4-((6-chloro-3-pyridinyl)sulfonyl)-1-(5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)-2-pyrimidinyl)-2-piperazinyl)methyl)-N-phenylmethanesulfonamide (0.134 g) as a white solid.

Workup

  1. concentrationconcentrated
  2. stirringthe mixture was stirred at room temperature for 10 min
  3. stirringthe mixture was stirred at room temperature for 1.5 h
  4. concentrationThe mixture was concentrated
  5. custompurified by column chromatography (50 g of silica gel, 0 to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-4821ea8f1a5043ed8ba0c8cd98cfbe75
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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