Methanol → HCID 68635754, compound

HRID 1177605Notes

Reaction equation

HRID 1177605 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].[BH4-].[Na+].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 4311764Sodium borohydrideHCID 10964479tert-Butylsulfinamide, (R)-(+)-HCID 59174916HCID 59174916, compound

Product 1

HCID 68635754HCID 68635754, compound

Reagents, catalysts & solvents 3

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
70 °C

Procedure

1-(3-Fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)ethanone (0.577 g, 2.49 mmol) was added to a solution of (R)-(+)-2-methyl-2-propanesulfinamide (0.150 g, 1.24 mmol), titanium (iv) ethoxide (0.510 mL, 2.48 mmol) in THF (5 mL). The reaction mixture was heated to 70° C. for 23 h, At which time was cooled to −50° C. To the reaction mixture was added a suspension of sodium borohydride (0.187 g, 4.95 mmol) in 0.5 mL of THF also at −50° C., allowed to stir for 18 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 (R)-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. temperaturewas cooled to −50° C
  2. additionTo the reaction mixture was added
  3. temperatureThe reaction mixture was warmed to 0° C.
  4. customThe crude reaction mixture
  5. stirringwhile being stirred rapidly
  6. filtrationThe resulting suspension was filtered through a plug of celite
  7. washthe cake rinsed with EtOAc and MeOH
  8. additionthe residue diluted with EtOAc
  9. extractionextracted with brine
  10. dry with materialdried over MgSO4
  11. customThe crude reaction mixture
  12. concentrationwas concentrated in vacuo
  13. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-05fb9f39a172421ba190cc9b176a24a0
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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