Sodium Carbonate → HCID 117876256, compound

HRID 588472Notes

Reaction equation

HRID 588472 reaction equation
Br[C:2]1[C:11]([F:12])=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:13]=[C:14]([CH3:30])[N:15]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH:17]4[F:29])[C:5]=3[C:4]=2[CH:3]=1.[Cl:31][C:32]1[CH:33]=[C:34]([CH:42]=[CH:43][C:44]=1B1OC(C)(C)C(C)(C)O1)[O:35][C:36]1[N:41]=[CH:40][CH:39]=[CH:38][N:37]=1.C([O-])([O-])=O.[Na+].[Na+].CO.C(Cl)Cl>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:31][C:32]1[CH:33]=[C:34]([O:35][C:36]2[N:37]=[CH:38][CH:39]=[CH:40][N:41]=2)[CH:42]=[CH:43][C:44]=1[C:2]1[C:11]([F:12])=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:13]=[C:14]([CH3:30])[N:15]([C@H:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][C@@H:17]4[F:29])[C:5]=3[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 21226129Dichloromethane methanolHCID 117876211HCID 117876211, compoundHCID 125496369HCID 125496369, compound

Product 1

HCID 117876256HCID 117876256, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
90 °C

Procedure

tert-Butyl 4-(8-bromo-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidine-1-carboxylate (9 g, 0.018 mol) was dissolved in toluene:ethanol (8:2, 50 ml) in a 250 ml seal tube and degasified the reaction mixture with argon gas for 15 minutes. Tetrakis (2.1 g, 0.0018 mol) was added and degasified the reaction mixture with argon gas for 5 minutes, 2-(3-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)pyrimidine (8 g, 0.024 .mol), followed by 2M Na2CO3(5 ml) was added and finally degasified the reaction mixture with argon gas for 10 minutes. The resulting reaction mixture was heated 5 h at 90° C. The reaction was monitored by TLC (5% MeOH/DCM), after completion of reaction by TLC the reaction mixture poured into ice water and extracted with EtOAc (3×100 mL). The combined organic layers were washed water, brine solution, dried over sodium sulphate and evaporated under vacuum. The residue was purified by column chromatography on silica gel (0-3% MeOH/DCM) to afford (3S,4S)-tert-butyl 4-(8-(2-chloro-4-(pyrimidin-2-yloxy)phenyl)-7-fluoro-2-methyl-1H-imidazo[4,5-c]quinolin-1-yl)-3-fluoropiperidine-1-carboxylate, 4 (10.2 g, 95% yield). 1HNMR (CDCl3, 400 MHz): δ 9.28 (d, 1H), 8.68-8.60 (m, 2H), 8.34-8.31 (d, 0.8H), 8.17 (d, 0.2H), 8.09-8.02 (m, 1H), 7.58-7.44 (m, 2H), 7.30 (dd, 1H), 7.16-7.10 (m, 1H), 5.62-5.04 (m, 1H), 4.89-4.25 (m, 3H), 3.10-2.75 (m, 5H), 2.40-2.20 (m, 2H), 1.51 (s, 9H); LCMS: 98.99%, m/z=607.45 (M+1); HPLC: 96.89%, rt: 4.32 min.

Workup

  1. customseal tube
  2. customfor 15 minutes
  3. customfor 5 minutes
  4. additionwas added
  5. customfor 10 minutes
  6. customThe resulting reaction mixture
  7. customafter completion of reaction by TLC the reaction mixture
  8. extractionextracted with EtOAc (3×100 mL)
  9. washThe combined organic layers were washed water, brine solution
  10. dry with materialdried over sodium sulphate
  11. customevaporated under vacuum
  12. customThe residue was purified by column chromatography on silica gel (0-3% MeOH/DCM)

Sources & evidence

ORD record
ord-2ab51fbe1798411db44be7e25f098dd6
Source dataset
uspto-grants-2016_01
Patent number
US09227969B2

Reaction notes

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