Hydrochloric Acid → HCID 9870317, compound

HRID 731523Notes

Reaction equation

HRID 731523 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15][N:16]([CH:21]2[CH2:24][CH2:23][CH2:22]2)[CH:17]2[CH2:20][CH2:19][CH2:18]2)=[CH:9][CH:8]=1.B(OC(C)C)(OC(C)C)OC(C)C.[ClH:38].C(=O)([O-])[O-].[Na+].[Na+].[NH2:45][C:46]1[C:47]([C:53]([NH:55][C:56]2[CH:57]=[N:58][CH:59]=[CH:60][CH:61]=2)=[O:54])=[N:48][C:49](Br)=[CH:50][N:51]=1>O1CCCC1.C(Cl)Cl.C(OCC)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[ClH:38].[NH2:45][C:46]1[C:47]([C:53]([NH:55][C:56]2[CH:57]=[N:58][CH:59]=[CH:60][CH:61]=2)=[O:54])=[N:48][C:49]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][CH2:15][N:16]([CH:21]3[CH2:24][CH2:23][CH2:22]3)[CH:17]3[CH2:20][CH2:19][CH2:18]3)=[CH:9][CH:8]=2)=[CH:50][N:51]=1

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 10336229HCID 10336229, compoundHCID 104021623-Amino-6-bromo-N-pyridin-3-ylpyrazine-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 9870317HCID 9870317, compoundYield 53%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (0.97 mL, 1.55 mmol) was added dropwise over 20 min to a cooled (−78° C.) solution of N-[3-(4-bromophenyl)propyl]-N,N-dicyclobutylamine (0.10 g, 0.31 mmol) and triisopropyl borate (0.21 mL, 0.93 mmol) in anhydrous tetrahydrofuran (2 mL) under a nitrogen atmosphere. The reaction mixture was stirred for 2 h at −78° C. HCl (aq 3 M, 0.6 mL) was added to the reaction mixture and the mixture was allowed to warm to room temperature. Tetrahydrofuran (2 mL) was added, followed by sodium carbonate (1.1 g, 10.8 mmol), Pd(dppf)Cl2 (0.010 g, 12.2 μmol) and 3-amino-6-bromo-N-pyridin-3-ylpyrazine-2-carboxamide (0.10 g, 0.34 mmol). The mixture was heated to 65° C. for 15 h. The solvent was removed and purification by column chromatography on silica using a gradient methylene chloride to methylene chloride/methanol, (2:1), as the eluent gave a yellow solid. The solid was dissolved in methylene chloride (10 mL) and 1 M HCl in diethyl ether was added while stirring. The formed yellow precipitate was filtered and dried to give 75 mg (53% yield) of the title compound as yellow solid: 1H NMR (D2O, 400 MHz) δ 9.47 (s, 1H), 8.73 (s, 1H), 8.69 (d, J=8.6 Hz, 1H), 8.61 (d, J=5.6 Hz, 1H), 8.10 (dd, J=15, 6 Hz, 1H), 7.98 (d, J=9 Hz, 2H), 7.41 (d, J=9 Hz, 2H), 3.80 (m, 2H), 3.01 (m, 2H), 2.75 (m, 2H), 2.28 (m, 4H), 2.17 (m, 4H), 2.03 (m, 2H), 1.79 (m, 4H); MS (ESI) 457 m/z (M++1).

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe mixture was heated to 65° C. for 15 h
  3. customThe solvent was removed
  4. custompurification by column chromatography on silica using a gradient methylene chloride to methylene chloride/methanol, (2:1), as the eluent
  5. customgave a yellow solid
  6. stirringwhile stirring
  7. filtrationThe formed yellow precipitate was filtered
  8. customdried

Sources & evidence

ORD record
ord-08da76b126a545f08548e04de02923d2
Source dataset
uspto-grants-2009_09
Patent number
US07585853B2

Reaction notes

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