Water → HCID 118223429, compound

HRID 2200207Notes

Reaction equation

HRID 2200207 reaction equation
[NH2:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([CH:16]3[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[O:21]([C:28]([NH:30][C:31]1[CH:32]=[C:33]([CH:46]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:48]=1)[O:34][CH:35]1[CH2:38][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:36]1)=O)C1C=CC=CC=1.O.C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH:16]1([C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:19]=[CH:20][C:2]([NH:1][C:28]([NH:30][C:31]4[CH:32]=[C:33]([CH:46]=[C:47]([C:49]([F:51])([F:52])[F:50])[CH:48]=4)[O:34][CH:35]4[CH2:38][N:37]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:36]4)=[O:21])=[CH:3][CH:4]=3)[CH:12]=[CH:11][N:10]=2)=[O:15])[CH2:17][CH2:18]1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 90020528HCID 90020528, compoundHCID 118223413HCID 118223413, compound

Product 1

HCID 118223429HCID 118223429, compoundYield 69.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve N-[4-(4-aminophenoxy)-2-pyridyl]cyclopropanecarboxamide (186 mg, 0.69 mmol), tert-butyl 3-[3-(phenoxycarbonylamino)-5-(trifluoromethyl)phenoxy]azetidine-1-carboxylate (312 mg, 0.69 mmol) and DMAP (17 mg, 0.14 mmol) in DMF (10 mL), stir at 100° C. for 16 hrs. Cool the reaction, pour the mixture to water (50 mL), adjust pH=7 with saturated NaHCO3 solution, extract with EtOAc (15 mL×3). Combine the organic layers, wash with brine (100 mL), dry over anhydrous Na2SO4. Concentrate under reduced pressure to give the crude product. Purification by chromatography (silica gel, EtOAc:PE=1:1) affords the target compound (300 mg, 69%). MS: (M+1): 628.3.

Workup

  1. temperatureCool
  2. customthe reaction
  3. extractionextract with EtOAc (15 mL×3)
  4. washCombine the organic layers, wash with brine (100 mL)
  5. dry with materialdry over anhydrous Na2SO4
  6. concentrationConcentrate under reduced pressure
  7. customto give the crude product
  8. customPurification by chromatography (silica gel, EtOAc:PE=1:1)

Sources & evidence

ORD record
ord-d0bfdafc66f042909f35f3ed7ec1f2df
Source dataset
uspto-grants-2016_06
Patent number
US09359338B2

Reaction notes

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