1,2-Dimethoxyethane → HCID 118045293, compound

HRID 595872Notes

Reaction equation

HRID 595872 reaction equation
Br[C:2]1[C:3]([NH2:18])=[N:4][CH:5]=[C:6]([CH:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)[N:7]=1.[CH2:19]([NH:26][C:27]([C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][C:30]=1[F:38])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C>[NH2:18][C:3]1[C:2]([C:32]2[CH:33]=[CH:34][C:29]([C:27]([NH:26][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[O:28])=[C:30]([F:38])[CH:31]=2)=[N:7][C:6]([CH:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 44717404[4-(Benzylcarbamoyl)-3-fluorophenyl]boronic acidHCID 118045542HCID 118045542, compound

Product 1

HCID 118045293HCID 118045293, compoundYield 47%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To 3-bromo-5-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-amine (630 mg, 2.005 mmol) was added (4-(benzylcarbamoyl)-3-fluorophenyl)boronic acid (767 mg, 2.81 mmol), PdCl2(dppf)CH2Cl2 adduct (164 mg, 0.201 mmol), DME (9 mL) and then last sodium carbonate 2M (3.01 mL, 6.02 mmol). The reaction was microwaved at 115° C. for 12 min. To the reaction was added 400 mL of ethyl acetate washed with water (2×), dried with sodium sulfate, filtered and concentrated to residue. The crude was purified by silica gel chromatography using 40 gram column eluting with 20-100% ethyl acetate and heptane. The desired fractions were concentrated to constant mass to give 432 mg of the desired product as free base used as is, (47% yield). LCMS (m/z): 463.2 (MH+), 0.82 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 8.94-8.81 (m, 1H), 7.89 (s, 1H), 7.80-7.69 (m, 1H), 7.67-7.52 (m, 2H), 7.33 (d, J=4.3 Hz, 4H), 7.27-7.18 (m, 1H), 6.09 (s, 2H), 4.49 (d, J=5.9 Hz, 2H), 3.85 (s, 4H), 2.70-2.61 (m, 1H), 1.84-1.67 (m, 6H), 1.65-1.48 (m, 2H).

Workup

  1. customThe reaction was microwaved at 115° C. for 12 min
  2. washwashed with water (2×)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to residue
  6. customThe crude was purified by silica gel chromatography
  7. washeluting with 20-100% ethyl acetate and heptane
  8. concentrationThe desired fractions were concentrated to constant mass

Sources & evidence

ORD record
ord-93afce2e9c5d442587ca2bac5c76dd3c
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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