Hydrochloric Acid → HCID 10412815, compound

HRID 736611Notes

Reaction equation

HRID 736611 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([S:13]([NH:16][C@H:17]([CH3:21])[CH2:18][O:19][CH3:20])(=[O:15])=[O:14])=[CH:9][CH:8]=1.B(OC(C)C)(OC(C)C)OC(C)C.[ClH:35].C(=O)([O-])[O-].[Na+].[Na+].[NH2:42][C:43]1[C:44]([C:50]([NH:52][C:53]2[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=2)=[O:51])=[N:45][C:46](Br)=[CH:47][N:48]=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:35].[NH2:42][C:43]1[C:44]([C:50]([NH:52][C:53]2[CH:54]=[N:55][CH:56]=[CH:57][CH:58]=2)=[O:51])=[N:45][C:46]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][C@H:17]([CH3:21])[CH2:18][O:19][CH3:20])(=[O:15])=[O:14])=[CH:9][CH:8]=2)=[CH:47][N:48]=1

Participants

11

Reactant 6

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 7270102HCID 7270102, compoundHCID 104021623-Amino-6-bromo-N-pyridin-3-ylpyrazine-2-carboxamideHCID 178418339Butyllithium

Product 1

HCID 10412815HCID 10412815, compoundYield 35%

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 (1.3 mL, 2.1 mmol) was added dropwise over 30 min to a cooled (−78° C.) solution of 4-bromo-N-[(1R)-2-methoxy-1-methylethyl]benzenesulfonamide (0.125 g, 0.406 mmol) and triisopropyl borate (0.28 mL, 1.2 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen atmosphere. The reaction mixture was stirred for 2 h at −78° C. HCl (aq, 3 M, 0.81 mL) was added to the reaction mixture and the mixture was allowed to warm to room temperature. Sodium carbonate (0.516 g, 4.9 mmol) was added followed by Pd(dppf)Cl2 (16 mg, 20 μmol) and 3-amino-6-bromo-N-pyridin-3-ylpyrazine-2-carboxamide (0.143 g, 0.487 mmol). Tetrahydrofuran (10 mL) was added and the mixture was heated to 65° C. for 15 h. The solvent was removed and purification by column chromatography using 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 HCl in diethyl ether (1 M 2.5 ml) was added. A yellow precipitate was formed. Filtering and drying gave 73 mg (35% yield) of the title compound as yellow solid: 1H NMR (D2O, 400 Hz) δ 9.28 (s, 1H), 8.53 (s, 3H), 8.0 (m, 1H), 7.96 (d, J=8 Hz, 2H), 7.70 (d, J=8 Hz, 2H), 3.42 (m, 1H), 3.27 (m, 1H), 3.16 (s, 3H), 0.93 (d, J=7 Hz, 3H);

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
  5. customgave a yellow solid
  6. customA yellow precipitate was formed
  7. filtrationFiltering
  8. customdrying

Sources & evidence

ORD record
ord-ccf0720b519747ce932ea487c53ecc6c
Source dataset
uspto-grants-2009_09
Patent number
US07595319B2

Reaction notes

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