Cesium carbonate → {1-[4-Methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-pyrrolidin-2-ylmethyl}-carbamic acid tert-butyl ester

HRID 519089Notes

Reaction equation

HRID 519089 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][C:10]1[N:5]2[CH:6]([CH3:25])[C:7](=[O:24])[N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:32]1[CH2:36][CH2:35][CH2:34][CH:33]1[CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].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>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:25][CH:6]1[C:7](=[O:24])[N:8]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:9]=[C:10]2[CH2:11][O:12][C:13]3[CH:14]=[CH:15][C:2]([N:32]4[CH2:36][CH2:35][CH2:34][CH:33]4[CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:43])([CH3:42])[CH3:44])=[CH:3][C:4]=3[N:5]12

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 21834643Pyrrolidin-2-ylmethyl-carbamic acid tert-butyl esterHCID 867274626-Bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

Product 1

HCID 86727461{1-[4-Methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-pyrrolidin-2-ylmethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 6-bromo-4-methyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (Preparation #1, Step E, 0.050 g, 0.117 mmol), cesium carbonate (0.076 g, 0.235 mmol), tert-butyl (pyrrolidin-2-ylmethyl)carbamate (0.047 g, 0.235 mmol), Pd(OAc)2 (0.008 g, 0.035 mmol) and BINAP (0.022 g, 0.035 mmol) in toluene (2 mL) was heated at reflux overnight. The reaction mixture was cooled to ambient temperature, filtered and concentrated in vacuo to give crude tert-butyl ((1-(1-methyl-2-oxo-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)pyrrolidin-2-yl)methyl)carbamate as brown solid, which was used for next step without further purification.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2bfe2dd70e58467b908e8d119c3514ed
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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