Sodium borohydride → HCID 118318865, compound

HRID 921216Notes

Reaction equation

HRID 921216 reaction equation
[CH2:1]([O:4][C:5]1([CH3:46])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[N:17]=[C:18]([CH2:20][O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=4[CH2:30][CH2:31]C=C)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:34])[C:12]=2[C@H:35]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])[C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[BH4-].[Na+]>C(Cl)Cl.O>[C:42]([O:41][C@@H:35]([C:12]1[C:13]([CH3:34])=[N:14][C:15]2=[CH:19][C:18]3=[N:17][N:16]2[C:11]=1[N:8]1[CH2:9][CH2:10][C:5]([CH3:46])([O:4][CH2:1][CH2:2][CH2:3][CH2:31][CH2:30][C:24]2[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=2[CH2:22][O:21][CH2:20]3)[CH2:6][CH2:7]1)[C:36]([O:38][CH2:39][CH3:40])=[O:37])([CH3:44])([CH3:45])[CH3:43]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318867HCID 118318867, compound

Product 1

HCID 118318865HCID 118318865, compoundYield 75%

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)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.079 mmol) and Grubb's II catalyst (66.7 mg, 0.079 mmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (2.97 mg, 0.079 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, which was then purified by biotage, eluting with 20% EtOAc/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-{16-fluoro-4,25-dimethyl-11,24-dioxa-1,5,7,8-tetraazapentacyclo[23.2.2.16,9.02,7.013,18]triaconta-2,4,6(30),8,13(18),14,16-heptaen-3-yl}acetate (36 mg, 0.059 mmol, 75% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.33-7.27 (m, 1H), 6.95 (dd, J=10.3, 2.7 Hz, 1H), 6.85 (td, J=8.3, 2.7 Hz, 1H), 6.56 (s, 1H), 6.07 (s, 1H), 4.78-4.64 (m, 4H), 4.58 (t, J=11.2 Hz, 1H), 4.18-4.11 (m, 2H), 3.90 (t, J=11.0 Hz, 1H), 3.44 (d, J=5.1 Hz, 2H), 3.05 (d, J=11.5 Hz, 1H), 2.95-2.85 (m, 1H), 2.83-2.72 (m, 2H), 2.63 (s, 3H), 2.03-1.88 (m, 2H), 1.84-1.62 (m, 8H), 1.31-1.24 (m, 15H). LCMS (M+1)=611.4.

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 20% EtOAc/hexane

Sources & evidence

ORD record
ord-255a7aee1cf14dbc85e1dec1a19864c5
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

Loading…