Sodium borohydride → ethyl (2S)-2-(tert-butoxy)-2-{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

HRID 921205Notes

Reaction equation

HRID 921205 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]=[CH:25][C:24]=4[CH2:29][CH2:30][CH:31]=[CH2:32])[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)C=C.[BH4-].[Na+]>C(Cl)CCl.C1(C)C=C(C)C=C(C)C=1N1CCN(C2C(C)=CC(C)=CC=2C)C1=[Ru](Cl)(Cl)=CC1C=CC=CC=1OC(C)C>[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[CH2:9][CH2:10][C:5]([CH3:45])([O:4][CH2:1][CH2:32][CH2:31][CH2:30][CH2:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[CH2:22][O:21][CH2:20]3)[CH2:6][CH2:7]1)[C:35]([O:37][CH2:38][CH3:39])=[O:36])([CH3:44])([CH3:42])[CH3:43]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318858(S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118318855ethyl (2S)-2-(tert-butoxy)-2-{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}acetateYield 70.1%

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 111,2-DichloroethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(7-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(((2-(but-3-en-1-yl)benzyl)oxy)methyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (55 mg, 0.089 mmol) and (1,3-dimesitylimidazolidin-2-ylidene)(2-isopropoxybenzylidene)ruthenium(VI) chloride (5.57 mg, 8.89 μmol) in ClCH2CH2Cl (60 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (5 mL). Sodium borohydride (3.36 mg, 0.089 mmol) was added and the reaction 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 to obtain an oil, which was then purify by biotage, eluting with 20% EtOAc/hexane to obtain ethyl (2S)-2-(tert-butoxy)-2-{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 (37 mg, 70%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.38-7.15 (m, 4H), 6.57 (s, 1H), 6.07 (s, 1H), 4.82-4.69 (m, 4H), 4.59 (t, J=11.2 Hz, 1H), 4.28-4.12 (m, 2H), 3.91 (t, J=10.9 Hz, 1H), 3.44 (d, J=7.3 Hz, 2H), 3.05 (d, J=11.3 Hz, 1H), 2.89 (dd, J=14.2, 6.4 Hz, 1H), 2.78 (dd, J=13.8, 8.3 Hz, 2H), 2.63 (s, 3H), 2.03-1.89 (m, 2H), 1.88-1.64 (m, 8H), 1.28 (s, 3H), 1.25 (s, 9H), 1.24-1.19 (m, 3H). LCMS (M+1)=593.4.

Workup

  1. temperaturewas refluxed for 2 h
  2. concentrationIt was then concentrated
  3. dissolutionthe residue was dissolved in MeOH (5 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. customto obtain an oil, which
  10. customwas then purify by biotage
  11. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-f3de4a57c67a4865b126cbd870b168b6
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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