Sodium borohydride → HCID 118318880, compound

HRID 921236Notes

Reaction equation

HRID 921236 reaction equation
[CH2:1]([C:4]1[CH:44]=[C:43]([CH3:45])[CH:42]=[CH:41][C:5]=1[CH2:6][O:7][CH2:8][C:9]1[CH:40]=[C:12]2[N:13]=[C:14]([CH3:39])[C:15]([C@H:28]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[C:16]([N:17]3[CH2:22][CH2:21][C:20]([O:24][CH2:25][CH:26]=[CH2:27])([CH3:23])[CH2:19][CH2:18]3)[N:11]2[N:10]=1)C=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.O>[C:35]([O:34][C@@H:28]([C:15]1[C:14]([CH3:39])=[N:13][C:12]2=[CH:40][C:9]3=[N:10][N:11]2[C:16]=1[N:17]1[CH2:18][CH2:19][C:20]([CH3:23])([O:24][CH2:25][CH2:26][CH2:27][CH2:1][C:4]2[CH:44]=[C:43]([CH3:42])[CH:45]=[CH:41][C:5]=2[CH2:6][O:7][CH2:8]3)[CH2:21][CH2:22]1)[C:29]([O:31][CH2:32][CH3:33])=[O:30])([CH3:36])([CH3:38])[CH3:37]

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 118318881HCID 118318881, compound

Product 1

HCID 118318880HCID 118318880, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 178425456HCID 178425456, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of (S)-ethyl 2-(2-(((2-allyl-4-methylbenzyl)oxy)methyl)-7-(4-(allyloxy)-4-methylpiperidin-1-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (50 mg, 0.081 mmol) and Grubbs II catalyst (68.6 mg, 0.081 mmol) in DCM (50 mL) was refluxed for 2 h. It was then concentrated and the residue was dissolved in MeOH (2 mL). NaBH4 (3.06 mg, 0.081 mmol) was then 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. The residue was purified by biotage, eluting with 20% EtOAc/hexane to isolate ethyl (2S)-2-(tert-butoxy)-2-{4,16,24-trimethyl-11,23-dioxa-1,5,7,8-tetraazapentacyclo[22.2.2.16,9.02,7.013,18]nonacosa-2,4,6(29),8,13(18),14,16-heptaen-3-yl}acetate (30 mg, 0.051 mmol, 62.6% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.36-7.25 (m, 1H), 7.08-6.97 (m, 2H), 6.50 (s, 1H), 6.16 (s, 1H), 4.88 (s, 2H), 4.76-4.59 (m, 3H), 4.24-4.08 (m, 2H), 3.96 (t, J=11.0 Hz, 1H), 3.57-3.40 (m, 2H), 2.92 (d, J=11.0 Hz, 1H), 2.80-2.72 (m, 2H), 2.69-2.59 (m, 4H), 2.34 (s, 3H), 2.11-2.01 (m, 1H), 1.98-1.86 (m, 3H), 1.86-1.74 (m, 2H), 1.76-1.60 (m, 2H), 1.29-1.22 (m, 12H), 1.19 (t, J=7.2 Hz, 3H). LCMS (M+1)=593.5.

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. customThe residue was purified by biotage
  9. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-c2bd369a95b64c5d9606c402e711face
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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