Dichloromethane → HCID 86268487, compound

HRID 1848744Notes

Reaction equation

HRID 1848744 reaction equation
Br[C:2]1[CH:36]=[C:35]([F:37])[C:5]([CH2:6][N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][C:18]4[C:23]([F:24])=[CH:22][C:21]([CH3:25])=[CH:20][N:19]=4)[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]2[C:32]([OH:34])=[O:33])=[C:4]([F:38])[CH:3]=1.C(Cl)Cl.[F:42][C:43]([F:54])([F:53])[C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.C([O-])([O-])=O.[K+].[K+]>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].C1(C)C=CC=CC=1.CCO>[F:38][C:4]1[CH:3]=[C:2]([C:47]2[CH:48]=[CH:49][C:44]([C:43]([F:54])([F:53])[F:42])=[CH:45][CH:46]=2)[CH:36]=[C:35]([F:37])[C:5]=1[CH2:6][N:7]1[C:11]2[CH:12]=[C:13]([O:16][CH2:17][C:18]3[C:23]([F:24])=[CH:22][C:21]([CH3:25])=[CH:20][N:19]=3)[CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[C@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[C:32]([OH:34])=[O:33]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86268084HCID 86268084, compound

Product 1

HCID 86268487HCID 86268487, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a 5 mL microwave vial were added racemic cis-2-{1-(4-bromo-2,6-difluorobenzyl)-6-[(3-fluoro-5-methylpyridin-2-yl)methoxy]-1H-benzimidazol-2-yl}cyclohexanecarboxylic acid (40 mg, 0.07 mmol), Pd(dppf)Cl2.DCM (5.0 mg, 0.007 mmol), (4-(trifluoromethyl)phenyl)boronic acid (18 mg, 0.010 mmol), K2CO3 (0.2 mL, 1M in H2O), EtOH (0.67 mL) and toluene (0.3 mL). The mixture was heated at 110° Celsius for 1 h, cooled to RT, concentrated to dryness and purified using FCC to provide the title compound. MS (ESI): mass calcd. for C35H29F6N3O3, 653.21; m/z found, 654.3 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.19 (s, 1H), 7.78 (dd, J=40.8, 8.3, 4H), 7.56-7.33 (m, 4H), 7.04 (d, J=2.2, 1H), 6.87 (dd, J=8.8, 2.3, 1H), 5.63 (two d, J=16.3, 2H), 5.23-5.11 (m, 2H), 3.90 (d, J=4.6, 1H), 2.78-2.67 (m, 1H), 2.40-2.23 (m, 4H), 2.16-2.06 (m, 1H), 2.05-1.89 (m, 2H), 1.87-1.68 (m, 2H), 1.51-1.37 (m, 2H).

Workup

  1. temperaturecooled to RT
  2. concentrationconcentrated to dryness
  3. custompurified

Sources & evidence

ORD record
ord-b1705abf4c674725a08f50340aaab7da
Source dataset
uspto-grants-2015_02
Patent number
US08952177B2

Reaction notes

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