Sodium borohydride → HCID 118318872, compound

HRID 921223Notes

Reaction equation

HRID 921223 reaction equation
[CH2:1]([O:4][C:5]1([CH3:49])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][N:21]([CH2:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[CH2:33][CH2:34]C=C)[CH:22]4[CH2:24][CH2:23]4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:37])[C:12]=2[C@H:38]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[BH4-].[Na+]>C(Cl)Cl.O>[C:45]([O:44][C@@H:38]([C:12]1[C:13]([CH3:37])=[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]([CH3:49])([O:4][CH2:1][CH2:2][CH2:3][CH2:34][CH2:33][C:27]2[CH:28]=[C:29]([F:32])[CH:30]=[CH:31][C:26]=2[CH2:25][N:21]([CH:22]2[CH2:23][CH2:24]2)[CH2:20]3)[CH2:10][CH2:9]1)[C:39]([O:41][CH2:42][CH3:43])=[O:40])([CH3:46])([CH3:48])[CH3:47]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318871HCID 118318871, compound

Product 1

HCID 118318872HCID 118318872, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)-4-fluorobenzyl)(cyclopropyl)amino)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (45 mg, 0.067 mmol) and Grubb's II catalyst (5.65 mg, 6.66 μmol) in DCM (45 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (2.52 mg, 0.067 mmol) was added and the reaction mixture 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. It was then purified by biotage, eluting with 25% EtOac/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-{11-cyclopropyl-16-fluoro-4,25-dimethyl-24-oxa-1,5,7,8,11-pentaazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (35 mg, 0.054 mmol, 81% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.14 (dd, J=8.4, 6.1 Hz, 1H), 6.90 (dd, J=10.3, 2.8 Hz, 1H), 6.77 (td, J=8.4, 2.8 Hz, 1H), 6.48 (s, 1H), 6.10 (s, 1H), 4.58-4.48 (m, 1H), 4.28-4.21 (m, 1H), 4.18-4.12 (m, 1H), 4.04 (d, J=1.0 Hz, 2H), 3.96-3.83 (m, 2H), 3.62 (d, J=13.8 Hz, 1H), 3.44-3.33 (m, 2H), 3.06-2.98 (m, 1H), 2.90-2.72 (m, 3H), 2.68-2.60 (m, 3H), 2.03-1.85 (m, 3H), 1.79-1.62 (m, 8H), 1.30-1.21 (m, 19H). LCMS (M+1)=650.3.

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
  9. customIt was then purified by biotage
  10. washeluting with 25% EtOac/hexane

Sources & evidence

ORD record
ord-16a9bfa739fb440f9c9fba8f7b224e49
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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