Hydrochloric Acid → HCID 10391157, compound

HRID 736463Notes

Reaction equation

HRID 736463 reaction equation
C([Li])CCC.B(OC(C)C)(OC(C)C)OC(C)C.Br[C:20]1[CH:25]=[CH:24][C:23]([S:26]([N:29]2[CH2:33][CH2:32][CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1.[ClH:34].C(=O)([O-])[O-].[Na+].[Na+].[NH2:41][C:42]1[C:43]([C:49]([NH:51][CH2:52][CH2:53][N:54]2[CH2:59][CH2:58][O:57][CH2:56][CH2:55]2)=[O:50])=[N:44][C:45](Br)=[CH:46][N:47]=1>O1CCCC1.CO.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:34].[NH2:41][C:42]1[C:43]([C:49]([NH:51][CH2:52][CH2:53][N:54]2[CH2:59][CH2:58][O:57][CH2:56][CH2:55]2)=[O:50])=[N:44][C:45]([C:20]2[CH:25]=[CH:24][C:23]([S:26]([N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)(=[O:28])=[O:27])=[CH:22][CH:21]=2)=[CH:46][N:47]=1

Participants

10

Reactant 6

HCID 313Hydrochloric Acid2×HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 7386181-(4-Bromobenzene-1-sulfonyl)pyrrolidineHCID 10426742HCID 10426742, compoundHCID 178418339Butyllithium

Product 1

HCID 10391157HCID 10391157, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.6 mL, 2.6 mmol) was added dropwise over 10 min to a cooled solution (−78° C.) of triisopropyl borate (0.6 mL, 2.6 mmol), and 1-[(4-bromophenyl)sulfonyl]pyrrolidine (0.251 g, 0.86 mmol) in anhydrous tetrahydrofuran (10 mL) under an atmosphere of nitrogen. The resulting mixture was stirred at −78° C. for 1 h and the mixture was allowed to warm up to room temperature. Aqueous HCl (3 M, 1.4 mL, 4.3 mmol) was added and the mixture was stirred for 10 min followed by the addition of sodium carbonate (0.9 g, 8.6 mmol) and the stirring was continued for another 20 min. 3-Amino-6-bromo-N-(2-morpholin-4-ylethyl)pyrazine-2-carboxamide (0.20 g, 0.61 mmol), and tetrahydrofuran (4 mL) were added followed by addition of Pd(dppf)Cl2 (28 mg, 0.03 mmol) and the resulting mixture was heated at 65° C. for 17 h. The mixture was allowed to return to room temperature and the solvent was evaporated. The resulting residue was suspended in methanol, silica was added, and the solvent was evaporated. Purification by column chromatography on silica using methylene chloride/methanol/triethyl amine, (95:5:0.1), as the eluent gave the free base that was subsequently dissolved in hot methanol and treated with HCl (1 M in diethyl ether). The formed precipitate was filtered off and dried in vacuo to give 72 mg (26% yield) of the title compound as a yellow solid: 1H NMR (DMSO-d6, 400 MHz) δ 11.24 (br s, 1H), 9.28 (m, 1H), 8.98 (s, 1H), 8.49 (d, J=8 Hz, 2H), 7.83 (d, J=8 Hz, 2H), 3.97 (m, 2H), 3.87 (d, J=12 Hz, 2H), 3.78 (m, 2H), 3.55 (d, J=12 Hz, 2H), 3.15 (m, 6H), 1.65 (m, 4H); MS (ES) m/z 461 (M++1).

Workup

  1. temperatureto warm up to room temperature
  2. stirringthe mixture was stirred for 10 min
  3. waitthe stirring was continued for another 20 min
  4. temperaturethe resulting mixture was heated at 65° C. for 17 h
  5. customto return to room temperature
  6. customthe solvent was evaporated
  7. additionsilica was added
  8. customthe solvent was evaporated
  9. customPurification by column chromatography on silica
  10. customgave the free base that
  11. filtrationThe formed precipitate was filtered off
  12. customdried in vacuo

Sources & evidence

ORD record
ord-f909d4eeb4db48aea4ba57f3131c9267
Source dataset
uspto-grants-2009_09
Patent number
US07595321B2

Reaction notes

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