Sodium borohydride → HCID 118318874, compound

HRID 921226Notes

Reaction equation

HRID 921226 reaction equation
[CH2:1]([C:4]1[CH:5]=[C:6]([CH:42]=[CH:43][CH:44]=1)[CH2:7][O:8][CH2:9][C:10]1[CH:41]=[C:13]2[N:14]=[C:15]([CH3:40])[C:16]([C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:17]([N:18]3[CH2:23][CH2:22][C:21]([O:25][CH2:26][CH:27]=[CH2:28])([CH3:24])[CH2:20][CH2:19]3)[N:12]2[N:11]=1)C=C.[BH4-].[Na+]>C(Cl)Cl.[NH4+].[Cl-]>[C:36]([O:35][C@@H:29]([C:16]1[C:15]([CH3:40])=[N:14][C:13]2=[CH:41][C:10]3=[N:11][N:12]2[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:24])([O:25][CH2:26][CH2:27][CH2:28][CH2:1][C:4]2[CH:5]=[C:6]([CH2:7][O:8][CH2:9]3)[CH:42]=[CH:43][CH:44]=2)[CH2:20][CH2:19]1)[C:30]([O:32][CH2:33][CH3:34])=[O:31])([CH3:38])([CH3:39])[CH3:37]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318873HCID 118318873, compound

Product 1

HCID 118318874HCID 118318874, compoundYield 42.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A mixture of (S)-ethyl 2-(2-(((3-allylbenzyl)oxy)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.083 mmol) and Grubb's II catalyst (70.2 mg, 0.083 mmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated. The residue was dissolved in MeOH (2 mL). Sodium borohydride (3.13 mg, 0.083 mmol) was added and the reaction was stirred at rt for 2 h. It was then diluted with NH4Cl, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated to obtain an oil, which was then purified by biotage, eluting with 20% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{4,23-dimethyl-11,22-dioxa-1,5,7,8-tetraazapentacyclo[21.2.2.16,9.113,17.02,7]nonacosa-2,4,6(29),8,13(28),14,16-heptaen-3-yl}acetate (20 mg, 0.035 mmol, 41.8% yield) as a white solid. LCMS (M+1)=579.7.

Workup

  1. temperaturewas refluxed for 2 h
  2. concentrationIt was then concentrated
  3. dissolutionThe residue was dissolved in MeOH (2 mL)
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain an oil, which
  9. customwas then purified by biotage
  10. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-9fdd393090b549efb42290f641fc0af5
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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