Cesium carbonate → HCID 131736367, compound

HRID 1055468Notes

Reaction equation

HRID 1055468 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]#[N:25])[C:10]=1[C:26]#[N:27].[CH3:28][N:29]([C@@H:37]([CH3:58])[C:38](=[O:57])[NH:39][C@H:40]1[C:46]2([CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)[O:45][C:44]2[CH:52]=[CH:53][CH:54]=[CH:55][C:43]=2[NH:42][C:41]1=[O:56])[C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN(C=O)C.[NH4+].[Cl-]>[C:26]([C:10]1[N:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:24]#[N:25])[C:12]2[C:17]([C:9]=1[CH2:8][N:42]1[C:41](=[O:56])[C@@H:40]([NH:39][C:38](=[O:57])[C@@H:37]([N:29]([CH3:28])[C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:35])[CH3:33])[CH3:58])[C:46]3([CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)[O:45][C:44]3[CH:52]=[CH:53][CH:54]=[CH:55][C:43]1=3)=[CH:16][CH:15]=[CH:14][CH:13]=2)#[N:27]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 90037186HCID 90037186, compoundHCID 90037528HCID 90037528, compound

Product 1

HCID 131736367HCID 131736367, compoundYield 96.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

Cs2CO3 (9.58 g, 29.4 mmol, Eq: 1.5) was added to a mixture of 3-(bromomethyl)-1-(2-cyanophenyl)-1H-indole-2-carbonitrile (9.89 g, 29.4 mmol, Eq: 1.5) and tert-butyl methyl((S)-1-oxo-1-((S)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)propan-2-yl)carbamate (8.5 g, 19.6 mmol, Eq: 1.00) in DMF (20 mL) and the mixture heated to 70° C. for 1 h. The mixture was cooled, diluted with sat. NH4Cl and extracted with EtOAc. The combined extracts were washed with H2O, dried over Na2SO4 and concentrated to give a material that was purified by silica gel chromatography to afford tert-butyl (S)-1-((S)-5-((2-cyano-1-(2-cyanophenyl)-1H-indol-3-yl)methyl)-4-oxo-2′,3′,4,5,5′,6′-hexahydro-3H-spiro[benzo[b][1,4]oxazepine-2,4′-pyran]-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (13 g, 96.3%) as a light yellow solid.

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with EtOAc
  3. washThe combined extracts were washed with H2O
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give a material that
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-fa878b7edb4840c59421e40e9ae21ce4
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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