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[ CAS No. 843663-66-1 ]

{[proInfo.proName]} (Synonyms:TMC27; R-2791) ,{[proInfo.pro_purity]}
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Chemical Structure| 843663-66-1
Chemical Structure| 843663-66-1
Structure of 843663-66-1 * Storage: {[proInfo.prStorage]}

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Product Details of [ 843663-66-1 ]

CAS No. :843663-66-1 MDL No. :MFCD14635354
Formula : C32H31BrN2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :N/A
M.W :555.50 g/mol Pubchem ID :-
Synonyms :

1. Bedaquiline

Safety of [ 843663-66-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 843663-66-1 ]

  • Downstream synthetic route of [ 843663-66-1 ]

[ 843663-66-1 ] Synthesis Path-Downstream   1~24

  • 2
  • rac-(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol [ No CAS ]
  • 6-bromo-α-[2-(dimethylamino)ethyl]-2-methoxy-α-1-naphthalenyl-β-phenyl-3-quinolineethanol*(11bR)-4-hydroxydinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepin 4-oxide [ No CAS ]
  • [ 843663-66-1 ]
YieldReaction ConditionsOperation in experiment
39% B. Isolation of the specific enantiomer (alphaS. betaR)-6-bromo-alpha-r2-(dimethylamino)ethyll- 2-methoxy-alpha-l-naphthalenyl-beta-phenyl-3-quinolineethanol from a mixture of stereoisomer^ forms by using f llbRV4-hvdroxydinaphtho[2,l-d:r.2'- firi,3,21dioxaphosphepin 4-oxide; The solid obtained under step C (30.45 g; 50 mmol; leq.) was suspended in acetone (193.3 g) at a temperature of 20 to 30 0C. This suspension was seeded with (alphaS, betaR)-6- EPO <DP n="23"/>bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-l-naphthalenyl-beta-phenyl-3- quinolineethanol * (1 lbR)-4-hydroxydinaphtho[2, 1 -d: 1 ' ,2 '-f] [ 1 ,3 ,2]dioxaphosphepin 4-oxide salt (9 mg; 0.016 mmol) obtained from previous preparation processes. (l lbR)-4-hydroxydinaphtho[2,l-d:l',2'-fl[l,3,2]dioxaphosphepin 4-oxide (17.60 g; 50 mmol; leq.) was dissolved in dimethylsulfoxide (38.7 g) at 40 to 500C and this solution was added via a filter to the above suspension in acetone within a time frame of 5 to 15 minutes. Then, the reaction mixture was seeded again with (alphaS, betaR) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(l-naphthyl)-beta-phenyl-3- quinolineethanol * (HbR)-4-hydroxydinaphtho[2,l-d:r,2'-fJ[l,3,2]dioxaphosphepin 4-oxide salt (9 mg; 0.016 mmol) obtained from previous preparation processes.The resulting suspension was stirred for 60 minutes (45 to 75 minutes), followed by heating to reflux. The suspension was stirred for 60 minutes (45 to 75 minutes) under reflux, followed by cooling to 25 0C (20 to 30 0C) in 30 to 60 minutes and stirring for 1 to 2 hours at 20 to 30 0C. The resulting solid was filtered off and washed twice with acetone (62.5g for each wash step). The resulting residue (59 g) was suspended in acetone (185.4 g) and the suspension was heated to reflux and stirred under reflux for 2 hours (1.5 to 2.5 hours) followed by cooling to 25 0C (20 to 30 0C) in 30 to 45 minutes and stirring for 45 to 75 minutes. The resulting solid was filtered off and washed with acetone (47 g) followed by washing with toluene (55 g). The obtained solid (54.96 g) was suspended in toluene (40.3 g) and treated (1.4 eq.) with a 10 % potassium carbonate solution (4.23 g K2CO3 in 38.02 g of purified water). The mixture was heated to 80-85 0C and the aqueous layer was separated.To the organic layer, a potassium carbonate solution (0.4 eq.) (1.23 g OfK2CO3 in 11.07 g of purified water) was added. After stirring for 5 to 15 minutes, the aqueous layer was separated and the organic layer was washed with purified water (11.8 g) at 80 to 85 0C.The organic layer was concentrated at 55 0C (50 to 60 0C) under vacuum.The residue was treated with ethanol (69 g) at a temperature > 45 to 500C followed by cooling within 0.5 to 1.5 hours to 0 to 50C and stirring for 0.5 to 1 hour at this temperature. The resulting solid was filtered off, washed twice with ethanol (18 g for each wash step) and dried in vacuo at 70 0C (65 to 75 0C). Yield : 39 % by weight (or 78% by weight calculated on the desired enantiomer) of (alphaS, betaR)-6-bromo-alpha-[2- (dimethylamino)ethyl]-2-methoxy-alpha-l-naphthalenyl-beta-phenyl-3-quinolineethanol (HPLC purity : > 99.6 %; enantiomeric excess > 99.8 %, m.p. 182-1840C). EPO <DP n="24"/>Purity was determined by HPLC using a YMC-Pack ODS-AQ (150 x 4.6 mm, 3 mum) column using as Mobile phase : Mobile phase A : water/trifluoroacetic acid (1000 ml/lml); Mobile phase B ; acetonitrile/trifluoroacetic acid (1000 ml/0.8 ml); eluent gradient starting with 75 % of A and 25 % of B?IO % of A and 90 % of B. Enantiomeric excess was determined by HPLC using a Cyclobond I RSP (250 x 4.6 mm) column using as mobile phase : MeOH/Water/ Ammonium acetate (60 ml/40 ml/0.154 g) adjusted to pH 7 with acetic acid. The obtained product (19.0 g) was suspended in toluene (10.96 g) and heated to 90 0C. The mixture was filtered in the heat and the filter was washed with toluene (1.5 g). The solution was cooled to 70 0C and ethanol (22.16 g) was added dropwise. During the addition of ethanol, the product started to crystallize (optionally a few mg of (alphaS, betaR) 6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-(l-naphthyl)-beta-phenyl-3- quinolineethanol may be added). A further ethanol (32.31 g) was added dropwise at 65 0C and the suspension was cooled to 00C and stirred for 1 hour. The residue was filtered off and washed with ethanol in 2 parts (52 g). The resulting product was dried (40 to 70 0C), yielding 17.07 g of (alphaS, betaR)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2- methoxy-alpha- 1 -naphthalenyl-beta-phenyl-3-quinolineethanol.
  • 3
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  • [ 110-17-8 ]
  • [ 845533-86-0 ]
YieldReaction ConditionsOperation in experiment
82% In isopropyl alcohol; at 20 - 70℃; for 18h;Heating / reflux; A. Synthesis of the fumarate salt of alphaS, betaR)-6-bromo-alpha-[2-fdimethylamino)ethyll- 2-methoxy-alpha- 1-naphthalenyl- beta-phenyl-3-q uinolineethanol; 1Og (0.018 mol) of (alphaS, betaR)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy-alpha-l- naphthalenyl-beta-phenyl-3-quinolineethanol and 2.13 g (0.018 mol) of fumaric acid were suspended in 185 ml isopropanol. Dicalite (0.25g) and charcoal (0.25g) were added to the suspension. The mixture was refluxed for an hour, the reaction mixture was cooled to 700C and filtered in the heat. The filter cake was washed with 10ml isopropanol.The mother liquor was slowly cooled to 500C and stirred for 1 hour at this temperature.The reaction mixture was further cooled to room temperature and stirred for 16 hours. The crystals were filtered off and washed with 20 ml isopropanol. The wet cake was dried at 500C during 16 hours.Yield: 1O g of (alpha S, beta R)-6-bromo-alpha-[2-(dimethylamino)ethyl]-2-methoxy- alpha-l-naphthalenyl-beta-phenyl-3-quinolineethanol (2E)-2-butenedioate (1 :1) (white solid) (82%).
In isopropyl alcohol; at 70 - 80℃; for 1h; Bedaquiline free base (1.19 g), fumaric acid (0.25 g), isopropanol (21 ml) were added into a 100 ml single- necked flask, heated to 70-80 C. until the solution is clear, stirred with heat-preservation for 1 h. Solids were precipitated when the solution was cooled to 50-70 C., the temperature was decreased to 5 C. and the solution was stirred for 1 h, filtered, the filter cake was washed with 10 ml isopropanol, dried at 60 C., -0.1 MPa to obtain end-product <strong>[843663-66-1]bedaquiline</strong> fumarate (1.20 g, yield=84%), and it is used as crude material for each example.
  • 4
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  • [ 3132-99-8 ]
  • [ 1032266-07-1 ]
YieldReaction ConditionsOperation in experiment
37% Example A4 a. Preparation of intermediate 7Intermediate 7 (dia A) ftBuLi (1.6M in hexanes, 14.1 ml, 0.0225 mol) was added dropwise at -700C under nitrogen flow to a solution of compound 14 of WO2004/011436 (5.0 g, 9.0 mmol) inTHF (5 0 ml). The mixture was stirred for 2 hours at -700C then dry ice was added.The resulting mixture was stirred lhour at -700C then water was added. The precipitate was filtered off, washed with water, CH3OH then CH3CH2OH and dried under vacuum. Yield: 0.8 g of intermediate 7 (17 %). A second fraction was obtained from the filtrate. Yield: 1.3 g of intermediate 7 (28%).
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  • [ 941-98-0 ]
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  • 20
  • rac-(1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol [ No CAS ]
  • [ 843663-66-1 ]
  • [ 654655-80-8 ]
YieldReaction ConditionsOperation in experiment
0.35 g Diastereomer 5A (1.0g) was suspended in acetone and the solution of (R)-(-)-BNP ACID (1eq) in DMSO was added. The suspension was stirred and refluxed for 1h, then cooled to room temperature and stirred for another 1h. The suspended solid was filtered and washed by acetone, then recrystallized by ethanol and water. After filtration, the solid was suspended in the solution of toluene and 10% K2CO3 (aq), and the mixture was stirred at 80C for half an hour. The aqueous phase was extracted with toluene, and the organic layers was washed with brine and dried over Na2SO4 . After filtration and evaporation under reduced pressure, the residue was stirred in ethanol under 0C. White solid which precipitates was separated with filtration, and air dried to give 0.35g of bedaquiline, m.p. 170-175C.
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  • (1R,2S)-1-(6-bromo-2-methoxy-3-quinolyl)-4-dimethylamino-2-(1-naphthyl)-1-phenylbutan-2-ol sulphate [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With sulfuric acid; In isopropyl alcohol; (1 R,2S)- 1 -(6-Bromo-2-methoxy-3 -quinolyl)-4-dimethylamino-2-( 1 -naphthyl)- 1 -phenyl-butan- 2-ol in the amount of 100 mg (0.18 mmol) was suspended in 14 ml of isopropyl alcohol. 18.4 mg (0.18 mmol) of sulphuric acid (96%) was added to this suspension. The resulting solution was slowly concentrated by partial evaporation of the solvent (about 7 ml) at the room temperature. The separated crystalline product was removed by filtration and dried at 30 to 40C. Yield 39 mg (33%). Melting point 188 C (DSC). XRPD: Fig. 6
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Similar Product of
[ 843663-66-1 ]

Chemical Structure| 845533-86-0

A648653[ 845533-86-0 ]

(1R,2S)-1-(6-Bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalen-1-yl)-1-phenylbutan-2-ol fumarate

Reason: Free-Salt