Sodium Carbonate → HCID 67216242, compound

HRID 2036040Notes

Reaction equation

HRID 2036040 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([OH:25])[C:15]3[N:11]([CH:12]=[N:13][CH:14]=3)[C@@H:10]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][C:17]=3[F:24])[CH2:9]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:32][O:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1>COCCOC.O.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]>[F:24][C:17]1[CH:18]=[C:19]([CH:22]=[CH:23][C:16]=1[C@@H:10]1[N:11]2[CH:12]=[N:13][CH:14]=[C:15]2[C@@:8]([OH:25])([C:5]2[CH:6]=[CH:7][C:2]([C:37]3[CH:38]=[CH:39][C:34]([O:33][CH3:32])=[CH:35][CH:36]=3)=[CH:3][CH:4]=2)[CH2:9]1)[C:20]#[N:21]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 67216898HCID 67216898, compound

Product 1

HCID 67216242HCID 67216242, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 4-[(5R,7S)-7-(4-bromo-phenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluoro-benzonitrile (25 mg, 63 μmol) in DME:H2O (4:1, 1 ml) were added Na2CO3 (10 mg, 94 μmol) and 4-methoxyphenylboronic acid (10.5 mg, 69 μmol). To this stirred mixture, PdCl2(dppf).CH2Cl2 complex (1.03 mg, 1.26 μmol) was added. The reaction was carried out under sealed-vessel microwave heating at 120° C. for 10 minutes using a Biotage Initiator™ (pre-stirring: 10 s, absorption level: very high). Upon completion, the mixture was allowed to cool to room temperature, the Pd catalyst was filtered off and the solvent was removed. The crude product obtained was purified using preparative LC-MS and lyophilized to give 3-fluoro-4-[(5R,7S)-7-hydroxy-7-(4′-methoxy-biphenyl-4-yl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-benzonitrile (13 mg, >95% purity). MS 426.0 (M+H), LCMS condition C, retention time 2.06 min. 1H NMR (600 MHz, DMSO-d6) δ ppm 2.90 (dd, 1H), 3.43-3.48 (m, 1H), 3.78 (s, 3H), 6.17 (dd, 1H), 6.59 (br. s., 1H), 7.01-7.03 (m, 2H), 7.33 (t, 1H), 7.53 (d, 2H), 7.60-7.62 (m, 2H), 7.63-7.65 (m, 2H), 7.78 (dd, 1H), 8.02 (dd, 1H), 8.94 (br. s., 1H).

Workup

  1. additionCH2Cl2 complex (1.03 mg, 1.26 μmol) was added
  2. customThe reaction was carried out under sealed-vessel
  3. custom10 s, absorption level
  4. temperatureto cool to room temperature
  5. filtrationthe Pd catalyst was filtered off
  6. customthe solvent was removed
  7. customThe crude product obtained
  8. customwas purified

Sources & evidence

ORD record
ord-b76ceb6ba80b4b089942a83fef5136a7
Source dataset
uspto-grants-2013_11
Patent number
US08575160B2

Reaction notes

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