Sodium borohydride → N-(4-(3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide

HRID 1177504Notes

Reaction equation

HRID 1177504 reaction equation
[Cl-].[Cl-].[Ca+2].[C:4]([NH:7][C:8]([CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:28][C:29]3[C:34]([N:35]=2)=[CH:33][CH:32]=[C:31]([C:36]2([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH2:38][CH2:37]2)[N:30]=3)=[C:23]([F:45])[CH:22]=1)([C:14](OCC)=[O:15])[C:9](OCC)=[O:10])(=[O:6])[CH3:5].[BH4-].[Na+]>O.CCO>[F:45][C:23]1[CH:22]=[C:21]([CH2:20][CH2:19][C:8]([NH:7][C:4](=[O:6])[CH3:5])([CH2:9][OH:10])[CH2:14][OH:15])[CH:26]=[CH:25][C:24]=1[C:27]1[S:28][C:29]2[C:34]([N:35]=1)=[CH:33][CH:32]=[C:31]([C:36]1([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[CH2:38][CH2:37]1)[N:30]=2

Participants

6

Reactant 3

HCID 4311764Sodium borohydride2×HCID 5284359Calcium ChlorideHCID 67111679Diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate

Product 1

HCID 67111774N-(4-(3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To solution of CaCl2 (0.188 g, 1.70 mmol) in 1.3 mL water was added a slurry of diethyl 2-acetamido-2-(2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethyl)malonate (0.400 g, 0.678 mmol) in about 15 mL EtOH total. To this slurry was added NaBH4 (0.128 g, 3.39 mmol). The mixture bubbled and became warm, and was cooled briefly with an ice bath, then allowed to stir at ambient temperature overnight. 10 mL THF was added, followed by additional NaBH4 (0.128 g, 3.39 mmol). After 5 h, the reaction mixture was concentrated in vacuo, partitioned between DCM and 1N aq. HCl, and extracted with DCM. The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The material was treated with 10% MeOH in DCM and adsorbed onto 2 g silica gel, dried, and passed through a Redi-Sep® pre-packed silica gel column (40 g) using 0-10% MeOH/DCM. The product-containing fractions were concentrated to give N-(4-(3-fluoro-4-(5-(1-phenyl-cyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)-1-hydroxy-2-(hydroxymethyl)butan-2-yl)acetamide as a white solid. MS (ESI) m/z: calculated: 505.2; Observed: 506.0 (M++1).

Workup

  1. customThe mixture bubbled
  2. temperaturebecame warm
  3. temperaturewas cooled briefly with an ice bath
  4. addition10 mL THF was added
  5. waitAfter 5 h
  6. concentrationthe reaction mixture was concentrated in vacuo
  7. custompartitioned between DCM and 1N aq. HCl
  8. extractionextracted with DCM
  9. dry with materialThe combined organics were dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. additionThe material was treated with 10% MeOH in DCM
  13. customdried
  14. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-a5e4e5123aab488da8e73a3ce43a30b8
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

Loading…