Ammonia → HCID 67167593, compound

HRID 1506541Notes

Reaction equation

HRID 1506541 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[S:17][C:18]4[C:28]5[C:23](=[CH:24][C:25]([CH:29]6[CH2:33][CH2:32][C:31](=O)[CH2:30]6)=[CH:26][CH:27]=5)[CH2:22][CH2:21][C:19]=4[N:20]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[NH3:37].[CH2:38](B1OC(C)(C)C(C)(C)O1)[CH:39]=[CH2:40]>ClCCl>[CH2:38]([C:31]1([NH2:37])[CH2:32][CH2:33][CH:29]([C:25]2[CH:24]=[C:23]3[C:28](=[CH:27][CH:26]=2)[C:18]2[S:17][C:16]([C:10]4[O:9][N:8]=[C:7]([C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:11]=4[C:12]([F:14])([F:15])[F:13])=[N:20][C:19]=2[CH2:21][CH2:22]3)[CH2:30]1)[CH:39]=[CH2:40]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 887MethanolHCID 27631714,4,5,5-Tetramethyl-2-(prop-2-en-1-yl)-1,3,2-dioxaborolane2×HCID 67171836HCID 67171836, compound

Product 1

HCID 67167593HCID 67167593, compoundYield 47.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 3-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)cyclopentanone (prepared according to Preparation 121C from 5-(7-iodo-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)-3-phenyl-4-(trifluoromethyl)isoxazole (Preparation 123A), 200 mg, 0.416 mmol), 7 M methanol solution of ammonia (2 mL, 14.00 mmol), and anhydrous dichloromethane (1.5 mL) was added allylboronic acid pinacol ester (0.117 mL, 0.624 mmol). The mixture was stirred at room temperature overnight. More allylboronic acid pinacol ester (0.1 mL) was added. The mixture was stirred at room temperature for 5 h before being concentrated. The residue was mixed with water (5 mL) and extracted with dichloromethane (4×2 mL). The combined dichloromethane extracts were dried (sodium sulfate) and concentrated under reduced pressure. Purification using reverse phase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, neutralization with saturated aqueous sodium bicarbonate solution and extraction with dichloromethane gave 1-allyl-3-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)cyclopentanamine (103 mg, 0.197 mmol, 47.4% yield) as a glassy solid. The compound had an HPLC retention time=3.75 min. (condition C); LC/MS M+1=521.9.

Workup

  1. stirringThe mixture was stirred at room temperature for 5 h
  2. concentrationbefore being concentrated
  3. additionThe residue was mixed with water (5 mL)
  4. extractionextracted with dichloromethane (4×2 mL)
  5. dry with materialThe combined dichloromethane extracts were dried (sodium sulfate)
  6. concentrationconcentrated under reduced pressure
  7. customPurification
  8. concentrationphase HPLC (Phenomenex Luna AXIA 5 u c18 30×100 mm, 10 min. run, solvent A: 10% MeOH: 90% H2O: 0.1% TFA, solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, neutralization
  9. extractionwith saturated aqueous sodium bicarbonate solution and extraction with dichloromethane

Sources & evidence

ORD record
ord-dc732341582844a5afd2ea2e8e308dbd
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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