Dichloromethane → HCID 90414326, compound

HRID 1776770Notes

Reaction equation

HRID 1776770 reaction equation
BrC1C=CC=C(CBr)C=1.Br[C:11]1[CH:12]=[C:13]([CH:45]=[CH:46][CH:47]=1)[CH2:14][N:15]1[C:19]2[CH:20]=[CH:21][C:22]([O:24][CH2:25][C:26]3[CH:35]=[CH:34][C:33]4[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=4)[N:27]=3)=[CH:23][C:18]=2[N:17]=[C:16]1[CH2:36][C:37]([CH3:44])([CH3:43])[C:38]([O:40][CH2:41][CH3:42])=[O:39].[CH3:48][O:49][C:50]1[N:55]=[CH:54][C:53](B(O)O)=[CH:52][CH:51]=1.C(Cl)Cl.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]>[CH3:48][O:49][C:50]1[N:55]=[CH:54][C:53]([C:11]2[CH:12]=[C:13]([CH:45]=[CH:46][CH:47]=2)[CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][C:22]([O:24][CH2:25][C:26]4[CH:35]=[CH:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:27]=4)=[CH:23][C:18]=3[N:17]=[C:16]2[CH2:36][C:37]([CH3:44])([CH3:43])[C:38]([OH:40])=[O:39])=[CH:52][CH:51]=1.[CH3:48][O:49][C:50]1[N:55]=[CH:54][C:53]([C:11]2[CH:12]=[C:13]([CH:45]=[CH:46][CH:47]=2)[CH2:14][N:15]2[C:19]3[CH:20]=[CH:21][C:22]([O:24][CH2:25][C:26]4[CH:35]=[CH:34][C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[N:27]=4)=[CH:23][C:18]=3[N:17]=[C:16]2[CH2:36][C:37]([CH3:43])([CH3:44])[C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:52][CH:51]=1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 699793-Bromobenzyl bromideHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 90414392HCID 90414392, compound

Product 2

HCID 90414326HCID 90414326, compoundHCID 90416498HCID 90416498, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

The title compound was prepared using similar methods to those in Example 33 using 1-bromo-3-(bromomethyl)benzene in Step A and by inserting the following procedure between Step E and F. To a 5 mL microwave vial were added a stirbar, ethyl 3-(1-(3-bromobenzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoate (230 mg, 0.4 mmol), 6-methoxypyridin-3-ylboronic acid (92 mg, 0.6 mmol), Pd(dppf)Cl2.CH2Cl2 (29 mg, 0.04 mmol), and K2CO3 (221 mg, 1.6 mmol). The vial was capped and flushed with nitrogen before adding 8 mL of N2 sparged 1,4-dioxane and 2 mL of N2 sparged water. The resulting mixture was heated at 80° C. for 12 hours. The vial was cooled to RT, concentrated to dryness, and subjected to FCC purification to afford ethyl 3-(1-(3-(6-methoxypyridin-3-yl)benzyl)-5-(quinolin-2-ylmethoxy)-1H-benzo[d]imidazol-2-yl)-2,2-dimethylpropanoate. MS (ESI): mass calcd. for C37H36N4O4, 600.27; m/z found, 601.1 [M+H]+. The title compound was then prepared using similar methods to those in Example 33 Step F to afford the title compound. MS (ESI): mass calcd. for C35H32N4O4, 572.24; m/z found, 573.3 [M+H]+. 1H NMR (300 MHz, DMSO-d6) δ 12.21 (s, 1H), 8.43-8.32 (m, 2H), 8.02 (d, J=8.5, 1H), 7.97 (d, J=8.3, 1H), 7.90 (dd, J=8.7, 2.5, 1H), 7.81-7.73 (m, 1H), 7.67 (d, J=8.5, 1H), 7.60 (t, J=7.4, 1H), 7.53 (d, J=6.9, 1H), 7.45-7.31 (m, 3H), 7.18 (d, J=1.6, 1H), 6.98-6.85 (m, 3H), 5.52 (s, 2H), 5.36 (s, 2H), 3.87 (s, 3H), 3.07 (s, 2H), 1.25 (s, 6H).

Workup

  1. customThe vial was capped
  2. customflushed with nitrogen
  3. additionbefore adding 8 mL of N2
  4. customsparged 1,4-dioxane and 2 mL of N2
  5. customsparged water
  6. temperatureThe vial was cooled to RT
  7. concentrationconcentrated to dryness
  8. customsubjected to FCC purification

Sources & evidence

ORD record
ord-1ae1c5bdef844af3b7861d1bd7b3230c
Source dataset
uspto-grants-2016_02
Patent number
US09265770B2

Reaction notes

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