Dimethylformamide → HCID 131736369, compound

HRID 1055471Notes

Reaction equation

HRID 1055471 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:16]([CH2:17][C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]#[N:34])[N:19]=3)[C:15](=[O:35])[C@@H:14]([NH:36][C:37](=[O:49])[C@@H:38]([N:40]([CH3:48])[C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH3:39])[C:8]3([CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[O:7][C:6]=2[CH:50]=1.[CH3:51][N:52](C=O)C>[NH4+].[Cl-].[C-]#N.[C-]#N.[Zn+2].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>[C:51]([C:2]1[CH:3]=[CH:4][C:5]2[N:16]([CH2:17][C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[C:33]#[N:34])[N:19]=3)[C:15](=[O:35])[C@@H:14]([NH:36][C:37](=[O:49])[C@@H:38]([N:40]([CH3:48])[C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH3:39])[C:8]3([CH2:9][CH2:10][O:11][CH2:12][CH2:13]3)[O:7][C:6]=2[CH:50]=1)#[N:52]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 131736370HCID 131736370, compound

Product 1

HCID 131736369HCID 131736369, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of tert-butyl (S)-1-((S)-8-bromo-5-((1-(2-cyanophenyl)-1H-indazol-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 (50 mg, 67.2 μmol, Eq: 1.00) in DMF (1.5 mL) was degassed with argon and Zn(CN)2 (15.8 mg, 134 μmol, Eq: 2) and Pd(Ph3P)4 (23.3 mg, 20.2 μmol, Eq: 0.3) were added. The mixture was heated in microwave at 110° C. for 30 min., cooled, diluted with sat. NH4Cl and extracted with EtOAc. The combined extracts were washed with H2O, then concentrated and the residue was purified by preparative TLC to give tert-butyl (S)-1-((S)-8-cyano-5-((1-(2-cyanophenyl)-1H-indazol-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 (43.5 mg, 94%)

Workup

  1. additionwere added
  2. temperaturecooled
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with H2O
  5. concentrationconcentrated
  6. customthe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-3cc1a36f6f1b4a009efac1b533cbe73d
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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