Methanol → HCID 68636738, compound

HRID 1177607Notes

Reaction equation

HRID 1177607 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:26](=O)[CH3:27])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.[CH3:29][C:30]([S@:33]([NH2:35])=[O:34])([CH3:32])[CH3:31].CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].CO>C1COCC1.[Cl-].[Na+].O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[F:1][C:2]1[CH:3]=[C:4]([CH:26]([NH:35][S@:33]([C:30]([CH3:32])([CH3:31])[CH3:29])=[O:34])[CH3:27])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2

Participants

8

Reactant 4

HCID 887MethanolHCID 3611392Lithium tri-s-butylborohydrideHCID 10964479tert-Butylsulfinamide, (R)-(+)-2×HCID 59174916HCID 59174916, compound

Product 1

HCID 68636738HCID 68636738, compound

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalyst2×HCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

1-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)ethanone (0.48 g, 1.2 mmol) was added to a solution of (R)-(+)-2-methyl-2-propanesulfinamide ((0.150 g, 1.2 mmol), titanium (iv) ethoxide (0.510 mL, 2.48 mmol) in THF (5 mL). The reaction mixture was heated to 70° C. for 2 h at which point additional (R)-(+)-2-methyl-2-propanesulfinamide (0.150 g, 1.2 mmol) and titanium (iv) ethoxide (0.51 mL, 2.48 mmol) were added and the reaction mixture was allowed to stir for 18 h at 70° C. The reaction mixture was cooled to ambient temperature and then to −50° C. To the reaction mixture was added dropwise 1 M solution of L-Selectride (3.7 mL, 3.7 mmol) also at −50° C., and allowed to stir for 5 h at −50° C. The reaction mixture was warmed to 0° C. and MeOH was added dropwise until gas evolution was no longer observed. The crude reaction mixture was poured into an equal volume of brine while being stirred rapidly. The resulting suspension was filtered through a plug of celite, the cake rinsed with EtOAc and MeOH. The filtrate was reduced in vacuo, the residue diluted with EtOAc, extracted with brine and dried over MgSO4. The crude reaction mixture was concentrated in vacuo and purified by silica gel chromatography to afford (S)-N-(1-(3-fluoro-4-(5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridin-2-yl)phenyl)-ethyl)-2-methylpropane-2-sulfinamide. MS (ESI) m/z: calculated: 493.2; Observed: 494.0 (M++1).

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. customto −50° C
  4. stirringto stir for 5 h at −50° C
  5. temperatureThe reaction mixture was warmed to 0° C.
  6. customThe crude reaction mixture
  7. stirringwhile being stirred rapidly
  8. filtrationThe resulting suspension was filtered through a plug of celite
  9. washthe cake rinsed with EtOAc and MeOH
  10. additionthe residue diluted with EtOAc
  11. extractionextracted with brine
  12. dry with materialdried over MgSO4
  13. customThe crude reaction mixture
  14. concentrationwas concentrated in vacuo
  15. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-1e6c7effd18943c980a17711c0de47c2
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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