Sodium hydride → (2S,4R)-1-(tert-butoxycarbonyl)-4-(4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)pyrrolidine-2-carboxylic acid

HRID 1177577Notes

Reaction equation

HRID 1177577 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:20]1[CH:25]=[CH:24][C:23]([C:26]2[S:27][C:28]3[C:33]([N:34]=2)=[CH:32][CH:31]=[C:30]([C:35]2([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[CH2:37][CH2:36]2)[N:29]=3)=[CH:22][CH:21]=1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[S:27][C:28]4[C:33]([N:34]=3)=[CH:32][CH:31]=[C:30]([C:35]3([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=5)[CH2:36][CH2:37]3)[N:29]=4)=[CH:24][CH:25]=2)[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 671116182-(4-Fluorophenyl)-5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine

Product 1

HCID 68636885(2S,4R)-1-(tert-butoxycarbonyl)-4-(4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)pyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A solution of (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid (162.1 mg, 0.701 mmol) in DMF (4.0 mL) was slowly added to a suspension of sodium hydride (60% w/w in mineral oil) (58 mg, 1.45 mmol) in DMF (4.0 mL), and the resulting mixture was heated at 95° C. for 5 min. 2-(4-Fluorophenyl)-5-(1-phenylcyclopropyl)-thiazolo[5,4-b]pyridine (75.3 mg, 0.217 mmol) was then added, and the resulting solution was heated at 95° C. for 18 h. The reaction mixture was subsequently cooled to 25° C. and diluted with EtOAc (5 mL). Excess NaH was quenched with water (5 mL), and the resulting mixture was diluted with 0.1N aq. HCl (40 mL) and extracted with EtOAc. The combined extracts were sequentially washed with water (50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to provide (2S,4R)-1-(tert-butoxycarbonyl)-4-(4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenoxy)pyrrolidine-2-carboxylic acid as a yellow solid. MS (ESI) m/z: Calculated: 557.2; Observed: 557.8 (M++1).

Workup

  1. temperaturethe resulting solution was heated at 95° C. for 18 h
  2. temperatureThe reaction mixture was subsequently cooled to 25° C.
  3. customExcess NaH was quenched with water (5 mL)
  4. additionthe resulting mixture was diluted with 0.1N aq. HCl (40 mL)
  5. extractionextracted with EtOAc
  6. washThe combined extracts were sequentially washed with water (50 mL) and brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-355467deb9ee4776bdda0d08049b2867
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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