Sodium borohydride → HCID 118318892, compound

HRID 921252Notes

Reaction equation

HRID 921252 reaction equation
[CH2:1]([C:4]1[CH:44]=[C:43]([F:45])[C:42]([F:46])=[CH:41][C:5]=1[CH2:6][O:7][CH2:8][C:9]1[CH:40]=[C:12]2[N:13]=[C:14]([CH3:39])[C:15]([C@H:28]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[C:16]([N:17]3[CH2:22][CH2:21][C:20]([O:24][CH2:25][CH:26]=[CH2:27])([CH3:23])[CH2:19][CH2:18]3)[N:11]2[N:10]=1)C=C.[BH4-].[Na+]>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.C(Cl)Cl>[C:35]([O:34][C@@H:28]([C:15]1[C:14]([CH3:39])=[N:13][C:12]2=[CH:40][C:9]3=[N:10][N:11]2[C:16]=1[N:17]1[CH2:18][CH2:19][C:20]([CH3:23])([O:24][CH2:25][CH2:26][CH2:27][CH2:1][C:4]2[CH:44]=[C:43]([F:45])[C:42]([F:46])=[CH:41][C:5]=2[CH2:6][O:7][CH2:8]3)[CH2:21][CH2:22]1)[C:29]([O:31][CH2:32][CH3:33])=[O:30])([CH3:37])([CH3:36])[CH3:38]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318890HCID 118318890, compound

Product 1

HCID 118318892HCID 118318892, compoundYield 62.8%

Reagents, catalysts & solvents 2

HCID 178425456HCID 178425456, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(2-(((2-allyl-4,5-difluorobenzyl)oxy)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (100 mg, 0.156 mmol) and Grubbs II catalyst (13.25 mg, 0.016 mmol) in DCM (100 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). Sodium borohydride (5.90 mg, 0.156 mmol) was added and stirred at rt for 1 h. It was then quenched with NH4Cl, extracted with EtOAc. The organic layer was washed with water, dried over MgSO4, filtered and concentrated. The residue was purified by biotage, eluting with 20% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{15,16-difluoro-4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetate (60 mg, 0.098 mmol, 62.5% yield) as a white solid. LCMS (M+1)=615.3.

Workup

  1. temperaturewas refluxed for 2 h
  2. concentrationIt was then concentrated
  3. dissolutionthe residue was dissolved in MeOH (2 mL)
  4. customIt was then quenched with NH4Cl
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with water
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by biotage
  11. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-536390a020b2459fb2e3aceec2444e13
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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