Ammonia → 1-Amino-3-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanecarbonitrile

HRID 1506535Notes

Reaction equation

HRID 1506535 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH:25]3[CH2:29][CH2:28][C:27](=O)[CH2:26]3)=[CH:19][CH:18]=5)[C:8]=2[C:31]([F:34])([F:33])[F:32])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[NH4+:36].[C-:37]#[N:38].[Na+].N>CO.ClCCl>[NH2:36][C:27]1([C:37]#[N:38])[CH2:28][CH2:29][CH:25]([C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[C:14]2=[N:15][O:16][C:12]([C:9]4[C:8]([C:31]([F:34])([F:33])[F:32])=[C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)[O:11][N:10]=4)=[C:13]2[CH2:24][CH2:23]3)[CH2:26]1

Participants

7

Reactant 4

HCID 222Ammonia2×HCID 8929Sodium CyanideHCID 25517Ammonium ChlorideHCID 671723633-(3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanone

Product 1

HCID 671713751-Amino-3-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanecarbonitrileYield 101%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanone (Preparation 121C, 230 mg, 0.495 mmol), ammonium chloride (79 mg, 1.486 mmol), sodium cyanide (72.8 mg, 1.486 mmol), 7 M methanol solution of ammonia (4.95 mL, 34.7 mmol) and dichloromethane (2 mL) was stirred at room temperature for 1 day. Additional 7 M methanol solution of ammonia (2 mL) was added and the mixture was stirred at room temperature for 2.5 days. The mixture was concentrated. The residue was partitioned between ethyl acetate (10 mL) and saturated aqueous sodium bicarbonate solution (3 mL). The aqueous layer was separated and extracted with ethyl acetate (2×1.5 mL). The combined ethyl acetate extracts were dried (sodium sulfate) and concentrated under reduced pressure to give 1-amino-3-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)cyclopentanecarbonitrile (245 mg, 0.500 mmol, 100% yield) as a glassy solid. The compound had an HPLC retention time=3.51 min. (condition C); LC/MS M+1=491.2.

Workup

  1. stirringthe mixture was stirred at room temperature for 2.5 days
  2. concentrationThe mixture was concentrated
  3. customThe residue was partitioned between ethyl acetate (10 mL) and saturated aqueous sodium bicarbonate solution (3 mL)
  4. customThe aqueous layer was separated
  5. extractionextracted with ethyl acetate (2×1.5 mL)
  6. dry with materialThe combined ethyl acetate extracts were dried (sodium sulfate)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-16f5effc695b4f7bb59ab8a6fb8246e8
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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