HCID 86722409, compound → HCID 86722411, compound

HRID 718803Notes

Reaction equation

HRID 718803 reaction equation
[CH2:1]([C@@:3]12[CH2:27][CH2:26][C@@:25]([C:29]#[CH:30])([OH:28])[CH2:24][C@H:4]1[CH2:5][CH2:6][CH2:7][C:8]1[C:9]2=[CH:10][C:11]2[CH:12]=[N:13][N:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15]=2[CH:16]=1)[CH3:2]>[Pd].C1COCC1>[CH2:29]([C@:25]1([OH:28])[CH2:24][C@H:4]2[CH2:5][CH2:6][CH2:7][C:8]3[C:9](=[CH:10][C:11]4[CH:12]=[N:13][N:14]([C:17]5[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=5)[C:15]=4[CH:16]=3)[C@:3]2([CH2:1][CH3:2])[CH2:27][CH2:26]1)[CH3:30]

Participants

4

Reactant 1

HCID 86722409HCID 86722409, compound

Product 1

HCID 86722411HCID 86722411, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of (3R,4aR,12bR)-12b-ethyl-3-ethynyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Ethynyl) (0.0331 g, 0.082 mmol) and THF (1.00 mL) was added to 10 wt % Pd/C (wet) (0.006 g). The mixture was placed under a hydrogen atmosphere using a balloon. After about 2 h, the hydrogen was evacuated. The mixture was filtered through Celite® rinsing with DCM (20 mL). The organic volatiles were removed under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 0-4% EtOAc in DCM. The fractions containing product were combined and concentrated under reduced pressure. The residue was dissolved in MeCN and MeOH, treated with water, and concentrated under reduced pressure to remove the organic volatiles. The mixture was frozen then lyophilized to afford (3R,4aR,12bR)-3,12b-diethyl-9-(4-fluorophenyl)-1,2,3,4,4a,5,6,7,9,12b-decahydrobenzo[6,7]cyclohepta[1,2-f]indazol-3-ol (11, R1=4-Fluorophenyl, R2=Ethyl, R3=Ethyl) (0.031 g, 91%) as an ivory solid. LC/MS, method 2, Rt=3.07 min, MS m/z 407 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.25 (s, 1H), 7.87 (s, 1H), 7.84-7.74 (m, 2H), 7.54 (s, 1H), 7.45-7.35 (m, 2H), 4.03 (s, 1H), 3.24-3.12 (m, 1H), 2.98-2.86 (m, 1H), 2.20-2.03 (m, 2H), 2.03-1.92 (m, 1H), 1.91-1.62 (m, 4H), 1.61-1.20 (m, 8H), 0.83 (t, J=7.3 Hz, 3H), 0.37 (t, J=7.1 Hz, 3H). Sign of rotation is positive.

Workup

  1. customthe hydrogen was evacuated
  2. filtrationThe mixture was filtered through Celite®
  3. washrinsing with DCM (20 mL)
  4. customThe organic volatiles were removed under reduced pressure
  5. customThe residue was purified on silica gel (4 g)
  6. additionThe fractions containing product
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeCN
  9. additionMeOH, treated with water
  10. concentrationconcentrated under reduced pressure
  11. customto remove the organic volatiles
  12. temperatureThe mixture was frozen

Sources & evidence

ORD record
ord-d87cfd57d72e4d888222d08944bbbe90
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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