Sodium borohydride → HCID 118318878, compound

HRID 921231Notes

Reaction equation

HRID 921231 reaction equation
[CH2:1]([O:4][C:5]1([CH3:51])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]([CH:36]4[CH2:38][CH2:37]4)[CH2:22][C:23]4[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][C:24]=4[O:30][C@H:31]([CH2:33][CH:34]=C)[CH3:32])[CH:19]=[C:15]3[N:14]=[C:13]([CH3:39])[C:12]=2[C@H:40]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:7][CH2:6]1)[CH:2]=C.[BH4-].[Na+]>C(Cl)Cl.O>[C:47]([O:46][C@@H:40]([C:12]1[C:13]([CH3:39])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:7][CH2:6][C:5]([CH3:51])([O:4][CH2:1][CH2:2][CH2:34][CH2:33][C@H:31]([CH3:32])[O:30][C:24]2[CH:25]=[C:26]([CH3:29])[CH:27]=[CH:28][C:23]=2[CH2:22][N:21]([CH:36]2[CH2:37][CH2:38]2)[CH2:20]3)[CH2:10][CH2:9]1)[C:41]([O:43][CH2:44][CH3:45])=[O:42])([CH3:50])([CH3:49])[CH3:48]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318877HCID 118318877, compound

Product 1

HCID 118318878HCID 118318878, compoundYield 83.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-((cyclopropyl(4-methyl-2-((S)-pent-4-en-2-yloxy)benzyl)amino)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (90 mg, 0.128 mmol) and Grubb's II catalyst (10.89 mg, 0.013 mmol) in DCM (80 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (4.85 mg, 0.128 mmol) was added and the reaction was stirred at rt for 1 h. It was then diluted with water, 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 25% EtOac/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-[(20S)-11-cyclopropyl-4,16,20,26-tetramethyl-19,25-dioxa-1,5,7,8,11-pentaazapentacyclo[24.2.2.16,9.02,7.013,18]hentriaconta-2,4,6(31),8,13(18),14,16-heptaen-3-yl]acetate (90 mg, 0.107 mmol, 83% yield) as a white solid. LCMS (M+1)=676.4.

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 25% EtOac/hexane

Sources & evidence

ORD record
ord-98efac9be6a24328868f68106f6e1468
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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