1,2-Dichloroethane → HCID 66665336, compound

HRID 221768Notes

Reaction equation

HRID 221768 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH2:9][O:10][CH2:11][CH2:12][C:13]([C:19]2[CH:24]=[C:23]([NH2:25])[CH:22]=[CH:21][C:20]=2[F:26])([C:15]([F:18])([F:17])[F:16])[N:14]=1)([CH3:4])([CH3:3])[CH3:2].[C:28]([C:30]1[CH:31]=[CH:32][C:33]([C:36](O)=[O:37])=[N:34][CH:35]=1)#[N:29].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH2:9][O:10][CH2:11][CH2:12][C:13]([C:19]2[CH:24]=[C:23]([NH:25][C:36]([C:33]3[CH:32]=[CH:31][C:30]([C:28]#[N:29])=[CH:35][N:34]=3)=[O:37])[CH:22]=[CH:21][C:20]=2[F:26])([C:15]([F:16])([F:18])[F:17])[N:14]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 124007345-Cyanopyridine-2-carboxylic acidHCID 66665843HCID 66665843, compound

Product 1

HCID 66665336HCID 66665336, compoundYield 94.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of [5-(5-amino-2-fluoro-phenyl)-5-trifluoromethyl-2,5,6,7-tetrahydro-[1,4]oxazepin-3-yl]-carbamic acid tert-butyl ester (50 mg, 0.128 mmol), 5-cyano-2-pyridinecarboxylic acid (28.4 mg, 0.192 mmol) and HOAT (31.3 mg, 0.230 mmol) in 0.5 mL DMF was cooled to 0-5° C. EDC (36.7 mg, 0.192 mmol) and DIPEA (33 mg, 0.256 mmol) were added. The resulting solution was allowed to warm up to rt over night. The reaction mixture was then partitioned between saturated aqueous NaHCO3 solution and EtOAc. The layers were washed with saturated aqueous NaHCO3 solution, brine and EtOAc. The combined organic layers were dried over MgSO4.H2O and evaporated. The crude product was purified on a silica gel column by eluting with hexane/EtOAc 4/1->3/1 to give 63.3 mg of the title compound as a white solid.

Workup

  1. customThe reaction mixture was then partitioned between saturated aqueous NaHCO3 solution and EtOAc
  2. washThe layers were washed with saturated aqueous NaHCO3 solution, brine and EtOAc
  3. dry with materialThe combined organic layers were dried over MgSO4.H2O
  4. customevaporated
  5. customThe crude product was purified on a silica gel column
  6. washby eluting with hexane/EtOAc 4/1->3/1

Sources & evidence

ORD record
ord-10ddb7f8125447269b1ef00af86ce669
Source dataset
uspto-grants-2012_06
Patent number
US08207164B2

Reaction notes

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