Triethylamine → HCID 72188986, compound

HRID 1487060Notes

Reaction equation

HRID 1487060 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH:3]([CH2:7][OH:8])[CH2:2]1.C(N(CC)CC)C.[CH3:16][C:17]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:18]=1[N:24]([CH2:35][CH:36]([CH3:38])[CH3:37])[S:25]([C:28]1[CH:33]=[CH:32][C:31](F)=[CH:30][CH:29]=1)(=[O:27])=[O:26].[Li+].C[Si]([N-][Si](C)(C)C)(C)C>O1CCCC1.C(OCC)(=O)C>[CH3:16][C:17]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][C:18]=1[N:24]([CH2:35][CH:36]([CH3:38])[CH3:37])[S:25]([C:28]1[CH:29]=[CH:30][C:31]([N:1]2[CH2:6][CH2:5][O:4][CH:3]([CH2:7][OH:8])[CH2:2]2)=[CH:32][CH:33]=1)(=[O:27])=[O:26]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733832Lithium HexamethyldisilazideHCID 3497988Morpholin-2-ylmethanolHCID 89479332HCID 89479332, compound

Product 1

HCID 72188986HCID 72188986, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of morpholin-2-ylmethanol (30 mg, 0.256 mmol) in tetrahydrofuran (THF) (3 mL) stirred under nitrogen at room temperature was added triethylamine (0.071 mL, 0.512 mmol) dropwise. The reaction mixture was stirred at room temperature for 10 minutes then N-(2,4-dimethylphenyl)-4-fluoro-N-isobutylbenzenesulfonamide (86 mg, 0.256 mmol) was added. The reaction mixture was stirred at room temperature overnight. LCMS analysis showed no product, so the solvent was removed under a stream of nitrogen and the crude treated with LiHMDS (1M in THF, 0.768 mL, 0.768 mmol) and THF (2 mL). The reaction vessel was sealed and heated by microwaves (Biotage Initiator) to 150° C. for 30 minutes. After cooling, LCMS analysis showed some conversion, so the reaction vessel was resealed and reheated by microwaves (Biotage Initiator) to 150° C. for a further 30 minutes. No further conversion was seen by LCMS, so ethyl acetate (10 mL) was added to the mixture and the organic phase washed with water (10 mL) then dried using a hydrophobic frit. Solvent was removed under a stream of nitrogen to give the crude product. The crude was purified by mass directed autoprep (ammonium carbonate modifier). The relevant fractions were concentrated under a stream of nitrogen to give the required product, 4 mg. LCMS [LCMS2] Rt 1.29 min, m/z (ES+) 433 (M+H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customso the solvent was removed under a stream of nitrogen
  3. customThe reaction vessel was sealed
  4. temperatureheated by microwaves (Biotage Initiator) to 150° C. for 30 minutes
  5. temperatureAfter cooling
  6. waitreheated by microwaves (Biotage Initiator) to 150° C. for a further 30 minutes
  7. additionwas added to the mixture
  8. washthe organic phase washed with water (10 mL)
  9. customthen dried
  10. customSolvent was removed under a stream of nitrogen
  11. customto give the crude product
  12. customThe crude was purified by mass
  13. concentrationThe relevant fractions were concentrated under a stream of nitrogen

Sources & evidence

ORD record
ord-72d1456fe01e476da64709fa541ebdcb
Source dataset
uspto-grants-2016_08
Patent number
US09428452B2

Reaction notes

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