Sodium borohydride → ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetate

HRID 921211Notes

Reaction equation

HRID 921211 reaction equation
[CH2:1]([O:4][C:5]1([CH3:45])[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][CH:26]=[C:25]([CH2:29][CH2:30][CH:31]=C)[CH:24]=4)[CH:19]=[C:15]3[N:14]=[C:13]([CH3:33])[C:12]=2[C@H:34]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:7][CH2:6]1)[CH:2]=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:41]([O:40][C@@H:34]([C:12]1[C:13]([CH3:33])=[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]([CH3:45])([O:4][CH2:1][CH2:2][CH2:31][CH2:30][CH2:29][C:25]2[CH:24]=[C:23]([CH2:22][O:21][CH2:20]3)[CH:28]=[CH:27][CH:26]=2)[CH2:10][CH2:9]1)[C:35]([O:37][CH2:38][CH3:39])=[O:36])([CH3:43])([CH3:42])[CH3:44]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318862(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318863ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetateYield 42%

Reagents, catalysts & solvents 2

HCID 178425456HCID 178425456, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((3-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.081 mmol) and Grubbs II catalyst (6.86 mg, 8.08 μmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (3 mL). NaBH4 (15.28 mg, 0.404 mmol) was added and the reaction mixture was stirred at rt for 1 h. It was then quenched with water, extracted with EtOAc. The organic layer was dried over MgSO4, filtered and concentrated. The residue was then purified by biotage, eluting with 25% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{4,24-dimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.113,17.02,7]triaconta-2,4,6(30),8,13(29),14,16-heptaen-3-yl}acetate (20 mg, 0.034 mmol, 41.8% yield) as a white solid. LCMS (M+1)=593.4. 1H NMR (400 MHz, CDCl3) δ 7.36-7.32 (m, 2H), 7.23-7.16 (m, 2H), 6.61 (s, 1H), 5.93 (s, 1H), 4.66 (s, 2H), 4.61-4.52 (m, 2H), 4.34 (td, J=12.3, 2.2 Hz, 1H), 4.27-4.16 (m, 2H), 3.85 (td, J=12.0, 2.2 Hz, 1H), 3.42-3.36 (m, 2H), 3.17 (d, J=11.7 Hz, 1H), 2.81 (dt, J=13.1, 6.3 Hz, 2H), 2.65-2.60 (m, 4H), 2.00 (dd, J=13.7, 2.2 Hz, 1H), 1.89 (dd, J=13.6, 2.1 Hz, 1H), 1.85-1.70 (m, 4H), 1.61-1.43 (m, 4H), 1.26-1.21 (m, 15H).

Workup

  1. temperaturewas refluxed for 2 h
  2. concentrationIt was then concentrated
  3. dissolutionthe residue was dissolved in MeOH (3 mL)
  4. customIt was then quenched with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was then purified by biotage
  10. washeluting with 25% EtOAc/hexane

Sources & evidence

ORD record
ord-2ebeef31f82045cd8194b5f7f235b5fd
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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