Cesium carbonate → (+/-) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate

HRID 921689Notes

Reaction equation

HRID 921689 reaction equation
Br[C:2]1[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[Si:19]([O:26][CH2:27][CH:28]1[CH2:33][NH:32][CH2:31][CH2:30][N:29]1[CH:34]1[CH2:37][O:36][CH2:35]1)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[Si:19]([O:26][CH2:27][CH:28]1[N:29]([CH:34]2[CH2:37][O:36][CH2:35]2)[CH2:30][CH2:31][N:32]([C:2]2[C:3]([Cl:18])=[C:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=2)[CH2:33]1)([C:22]([CH3:25])([CH3:23])[CH3:24])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86708481Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamateHCID 867085572-(((Tert-butyldimethylsilyl)oxy)methyl)-1-(oxetan-3-yl)piperazine

Product 1

HCID 86708559(+/-) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamateYield 62.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

(+/−) Tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (545 mg, 1.644 mmol), 2-(((tert-butyldimethylsilyl)oxy)methyl)-1-(oxetan-3-yl)piperazine (518 mg, 1.808 mmol), Pd2(dba)3 (151 mg, 0.164 mmol), BINAP (102 mg, 0.164 mmol), Cs2CO3 (1071 mg, 3.29 mmol), and Toluene (16 mL) were combined in a 2 dram vial. The vial was evacuated and backfilled with Ar 3×, and the reaction was heated at 105° C. for 18 h. The reaction was cooled to room temperature and diluted with MeOH. The solution was filtered through celite and the filtrate concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% EtOAc/Hex). (+/−) tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate (551 mg) was obtained as an orange glass.

Workup

  1. customThe vial was evacuated
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with MeOH
  4. filtrationThe solution was filtered through celite
  5. concentrationthe filtrate concentrated in vacuo
  6. customThe crude material was purified by flash column chromatography (0-50% EtOAc/Hex)

Sources & evidence

ORD record
ord-7d1f5dca00c24c53a041f7636aff2955
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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