Diisopropylethylamine → HCID 86670370, compound

HRID 1972499Notes

Reaction equation

HRID 1972499 reaction equation
C1(C(C2C=CC=CC=2)=[N:8][C:9]2[S:10][C:11]([S:14]([N:17]3[CH2:22][CH2:21][NH:20][C@@H:19]([CH2:23][CH:24]4[CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[CH2:18]3)(=[O:16])=[O:15])=[CH:12][CH:13]=2)C=CC=CC=1.Cl[C:37]1[N:42]=[CH:41][C:40]([C:43]([OH:52])([C:48]([F:51])([F:50])[F:49])[C:44]([F:47])([F:46])[F:45])=[CH:39][N:38]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[NH2:8][C:9]1[S:10][C:11]([S:14]([N:17]2[CH2:22][CH2:21][N:20]([C:37]3[N:38]=[CH:39][C:40]([C:43]([OH:52])([C:44]([F:45])([F:46])[F:47])[C:48]([F:50])([F:51])[F:49])=[CH:41][N:42]=3)[C@@H:19]([CH2:23][CH:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH2:18]2)(=[O:15])=[O:16])=[CH:12][CH:13]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 866703482-(2-Chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol2×HCID 86670369HCID 86670369, compound

Product 1

HCID 86670370HCID 86670370, compoundYield 44.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

In a 20-mL vial was charged with N-(diphenylmethylidene)-5-(((3S)-3-(tetrahydro-2H-pyran-4-ylmethyl)-1-piperazinyl)sulfonyl)-2-thiophenamine (170 mg, 0.334 mmol)), 2-(2-chloropyrimidin-5-yl)-1,1,1,3,3,3-hexafluoropropan-2-ol (187 mg, 0.667 mmol, Intermediate D), and Hünig's base (175 μL, 1.001 mmol), and dioxane (5 mL). The vial was sealed and heated to 90° C. for 16 h. Afterwards, the mixture was concentrated in vacuo. The crude material was dissolved in THF (20 mL) and 4 N HCl in dioxane (5 mL). The resulting mixture was stirred for 2 h at room temperature. The mixture was concentrated, absorbed onto silica gel, and purified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2) to give 2-(2-((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-2-(tetrahydro-2H-pyran-4-ylmethyl)-1-piperazinyl)-5-pyrimidinyl)-1,1,1,3,3,3-hexafluoro-2-propanol (88 mg).

Workup

  1. customThe vial was sealed
  2. concentrationAfterwards, the mixture was concentrated in vacuo
  3. dissolutionThe crude material was dissolved in THF (20 mL)
  4. concentrationThe mixture was concentrated
  5. customabsorbed onto silica gel
  6. custompurified via column chromatography (40 g silica gel, 0 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-01f35bddb84e4f6284eec45ff6c3927b
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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