Methanol → HCID 66743344, compound

HRID 1259355Notes

Reaction equation

HRID 1259355 reaction equation
Br[C:2]1[C:7](=[O:8])[NH:6][C:5]2[C:9]3([CH2:26][CH2:25][O:24][CH2:23]3)[N:10]([C:13]3[CH:14]=[N:15][N:16]([CH2:18][C:19]([F:22])([F:21])[F:20])[CH:17]=3)[C:11](=[O:12])[C:4]=2[C:3]=1[CH3:27].C(N(CC)CC)C.[H][H].CO>CCO.[Pd].C(Cl)Cl>[CH3:27][C:3]1[C:4]2[C:11](=[O:12])[N:10]([C:13]3[CH:14]=[N:15][N:16]([CH2:18][C:19]([F:22])([F:20])[F:21])[CH:17]=3)[C:9]3([CH2:26][CH2:25][O:24][CH2:23]3)[C:5]=2[NH:6][C:7](=[O:8])[CH:2]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 66743423HCID 66743423, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 66743344HCID 66743344, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

As shown in step 24-vi of Scheme 24, to a suspension of Compound 2078 (1.65 g, 3.690 mmol) in EtOH (50 mL) at 23° C. was added triethylamine (1.120 g, 1.543 mL, 11.07 mmol), followed by the addition of Pd/C (430 mg, 0.4041 mmol) (10 wt % dry basis, Degussa type, wet). The reaction vessel was evacuated and the reaction atmosphere replaced with hydrogen gas. After stirring for 16 hours, the reaction mixture was treated with MeOH and DCM (50 mL each) and then filtered through diatomaceous earth, which was subsequently washed with 4:1 DCM:MeOH (100 mL). The combined filtrate was concentrated under reduced pressure to provide 4-methyl-6-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]spiro[1H-pyrrolo[3,4-b]pyridine-7,3′-tetrahydrofuran]-2,5-dione as a white solid (Compound 2079, 2 g, triethylamine impurity), which was used as is in subsequent reactions: ESMS (M+H) 369.30; 1H NMR (DMSO-d6, 300 MHz) δ 8.16 (s, 1H), 7.80 (s, 1H), 6.34 (br s, 1H), 5.17 (q, J=9, 2H), 4.13 (d, J=12, 1H), 3.93 (m, 3H), 2.45 (s, 3H), 2.30 (m, 2H).

Workup

  1. customThe reaction vessel was evacuated
  2. customthe reaction atmosphere
  3. filtrationfiltered through diatomaceous earth, which
  4. washwas subsequently washed with 4:1 DCM
  5. concentrationThe combined filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-e6920a2a88d0432f9ea7697007c9bd93
Source dataset
uspto-grants-2013_06
Patent number
US08466288B2

Reaction notes

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