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[ CAS No. 1147108-99-3 ]

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Chemical Structure| 1147108-99-3
Chemical Structure| 1147108-99-3
Structure of 1147108-99-3 * Storage: {[proInfo.prStorage]}

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Product Details of [ 1147108-99-3 ]

CAS No. :1147108-99-3 MDL No. :MFCD11506701
Formula : C5H12ClNO Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W :137.61 g/mol Pubchem ID :42609646
Synonyms :

Safety of [ 1147108-99-3 ]

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

Application In Synthesis of [ 1147108-99-3 ]

  • Downstream synthetic route of [ 1147108-99-3 ]

[ 1147108-99-3 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 1147108-99-3 ]
  • 20,20-ethylenedioxy-5α-pregnan-2α,3α-epoxide [ No CAS ]
  • (2S,3S,5S,8R,9S,10S,13S,14S,17S)-10,13-Dimethyl-17-(2-methyl-[1,3]dioxolan-2-yl)-2-((S)-2-methyl-morpholin-4-yl)-hexadecahydro-cyclopenta[a]phenanthren-3-ol [ No CAS ]
  • 2
  • [ 1403663-12-6 ]
  • [ 1147108-99-3 ]
  • [ 1403663-10-4 ]
YieldReaction ConditionsOperation in experiment
69% With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 70℃; for 5h; (S)-2-Methylmorpholine*HCl (586 mg, 4.26 mmol, 0.74 equiv.), chloropyrimidin-one 3 (1.91 g, 5.79 mmol, 1 equiv.) and DIPEA (3.03 ml, 17.4 mmol, 3 equiv.) were dissolved in MeCN (9.84 ml) and the mixture was heated to 70 C. After 2.45 h additional (S)-2-Methylmorpholine*HCl (159 mg, 1.16 mmol, 0.2 equiv.) was added and the reaction was stirred for another 2.15 h. The mixture was cooled to rt, diluted with CH2Cl2 and washed with water. The organic layer was separated and concentrated. The crude was combined with additional crude made under the same conditions (totally 10.3 mmol of chloropyrimidin-one 3 was used). Purification by reversed phase (C18) liquid chromatography using MeCN: H2O/MeCN/NH3 (95:5:0.2) (15-55 % MeCN) as eluent gave S-21 (2.80 g, 69 %, calculated for the combined reactions). 1H-NMR (400 MHz, CDCl3) d: 7.96 - 7.84 (m, 2H), 7.83 (d, 1H), 7.56 - 7.52 (m, 2H), 7.46 (t, 1H), 7.34 - 7.22 (m, 1H), 4.99 (s, 2H), 4.76 (s, 1H), 3.90 - 3.66 (m, 7H), 3.55 - 3.38 (m, 2 H), 2.95 - 2.79 (m 1H), 2.59 (t, 1H), 1.10 (d, 3 H). (OH and NH-proton not observed) LCMS-ES+ (m/z): [M + H]+ calcd, 395; found, 395.
  • 3
  • [ 1296271-66-3 ]
  • [ 1147108-99-3 ]
  • methyl 8-bromo-2-((S)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate [ No CAS ]
  • 4
  • [ 32315-10-9 ]
  • (4S)-7-(2-methylpyridin-4-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]
  • [ 1147108-99-3 ]
  • ((S)-2-methylmorpholino)((4S)-7-(2-methylpyridin-4-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepin-5(2H)-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
32.4% Triphosgene (0.470 g, 1.585 mmol) was added to a stirred solution of triethylamine (1.105 mL, 7.93 mmol) and (4S)-7-(2-methylpyridin-4-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine (0.4 g, 1.585 mmol) in tetrahydrofuran (50 mL) at room temperature and stirred for 1 h and followed by addition of <strong>[1147108-99-3](S)-2-methylmorpholine hydrochloride</strong> (0.327 g, 2.378 mmol) and heated to 70 C. for 15 h. Cooled to room temperature and diluted with ethyl acetate (100 mL) and water (100 mL). The separated organic layer was washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude compound (TLC eluent: 10% MeOH in ethyl acetate; UV active; Rf0.4). Crude compound was purified through column chromatography using neutral alumina and eluted in 50% ethyl acetate in hexane to afford (S)-2-methylmorpholino)((4S)-7-(2-methylpyridin-4-yl)-3,4-dihydro-1,4-methanopyrido[2,3b][1,4]diazepin-5(2H)-yl)meth-anone (0.2 g, 0.514 mmol, 32.4% yield) as gummy compound, LCMS (m/z) 480.3 (M+H)+.
32.4% Triphosgene (0.470 g, 1.585 mmol) was added to a stirred solution of triethylamine (1.105 mL, 7.93 mmol) and (4,S)-7-(2-methylpyridin-4-yl)-2,3,4,5-tetrahydro-l,4-methanopyrido [2,3-b][l,4]diazepine (0.4g, 1.585 mmol) in tetrahydrofuran (50 mL) at room temperature and stirred for lh and followed by addition of (,S)-2-methylmorpholine hydrochloride (0.327 g, 2.378 mmol) and heated to 70 C for 15 h. Cooled to room temperature and diluted with ethyl acetate (100 mL) and water (100 mL). The separated organic layer was washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to get crude compound (TLC eluent: 10% MeOH in ethyl acetate; UV active; Rf~0.4). Crude compound was purified through column chromatography using neutral alumina and eluted in 50% ethyl acetate in hexane to afford (,S)-2-methylmorpholino)((4S)-7-(2-methylpyridin-4-yl)-3,4-dihydro-l,4- methanopyrido[2,3-b][l,4]diazepin-5(2H)-yl)meth-anone (0.2g, 0.514 mmol, 32.4 % yield) as gummy compound, LCMS (m/z) 480.3 (M+H)+.
  • 5
  • (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
  • [ 1147108-99-3 ]
  • (9S)-5-[(2S)-2-methylmorpholin-4-yl]-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.02,7]dodeca-2,4,6-triene-8-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
32.8% With palladium diacetate; caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 16h;Inert atmosphere; To a degassed solution of (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (700 mg, 2.210 mmol), (S)-2-methylmorpholine Hydrochloride (335 mg, 2.431 mmol), Cs2CO3 (1440 mg, 4.42 mmol) and 2-dicyclohexylphosphino-2?,4?,6?-triisopropylbiphenyl (421 mg, 0.884 mmol) in 1,4-dioxane (10 mL) was added Pd(OAc)2 (99 mg, 0.442 mmol) at RT. Then the reaction mixture was heated at 100 C. for 16 h. The reaction mixture was allowed to room temperature, quenched with 2×15 ml of water and extracted with 2×50 ml of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude compound. The crude product was purified by column chromatography to afford (4S)-7-((S)-2-methylmorpholino)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (285 mg, 0.725 mmol, 32.8% yield) as off white solid (TLC: Rf value: 0.3, 5% Methanol in DCM), LCMS (m/z): 383.28 [M+H]+. 1H NMR (400 MHz, DMSO-d6): delta 13.40 (s, 1H), 9.38 (d, J=1.4 Hz, 1H), 8.40-8.14 (m, 2H), 7.40 (d, J=8.6 Hz, 1H), 6.53 (d, J=8.6 Hz, 1H), 5.44 (dd, J=6.0, 3.1 Hz, 1H), 4.12 (s, 1H), 3.96 (ddd, J=11.5, 3.6, 1.4 Hz, 1H), 3.86 (d, J=12.8 Hz, 1H), 3.62 (dd, J=11.8, 2.8 Hz, 2H), 3.09 (dd, J=11.4, 8.4 Hz, 1H), 2.96 (s, 2H), 2.93-2.78 (m, 2H), 2.58 (dd, J=12.6, 10.4 Hz, 1H), 2.17 (s, 1H), 1.85 (dt, J=14.3, 7.3 Hz, 1H), 1.23 (d, J=6.2 Hz, 3H).
32.8% With palladium diacetate; caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 16h; To a degassed solution of (4,S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4- methanopyrido[2,3-£][l,4]diazepine-5(2H)-carboxamide (700 mg, 2.210 mmol), (S)-2- methylmorpholine Hydrochloride (335 mg, 2.431 mmol), Cs2C03 (1440 mg, 4.42 mmol) and 2-dicyclohexylphosphino-2', 4', 6'-triisopropylbiphenyl (421 mg, 0.884 mmol) in 1,4- dioxane (10 mL) was added Pd(OAc)2 (99 mg, 0.442 mmol) at RT. Then the reaction mixture was heated at 100 C for 16 h. The reaction mixture was allowed to room temperature, quenched with 2x15 ml of water and extracted with 2x50 ml of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain crude compound. The crude product was purified by column chromatography to afford (4)S)-7-(()S)-2-methylmo holino)-N-(pyrazin-2-yl)-3,4- dihydro-l,4-methanopyrido[2,3-^][l,4]diazepine-5(2H)-carboxamide(285 mg, 0.725 mmol, 32.8 % yield) as off white solid (TLC: Rf value: 0.3, 5% Methanol in DCM), LCMS (/// r): 383.28 [M+H]+.1H NMR (400 MHz, OMSO-d6): delta 13.40 (s, 1H), 9.38 (d, J = 1.4 Hz, 1H), 8.40 - 8.14 (m, 2H), 7.40 (d, J = 8.6 Hz, 1H), 6.53 (d, J= 8.6 Hz, 1H), 5.44 (dd, J = 6.0, 3.1 Hz, 1H), 4.12 (s, 1H), 3.96 (ddd, J = 11.5, 3.6, 1.4 Hz, 1H), 3.86 (d, J = 12.8 Hz, 1H), 3.62 (dd, J= 11.8, 2.8 Hz, 2H), 3.09 (dd, J = 11.4, 8.4 Hz, 1H), 2.96 (s, 2H), 2.93 - 2.78 (m, 2H), 2.58 (dd, J = 12.6, 10.4 Hz, 1H), 2.17 (s, 1H), 1.85 (dt, J= 14.3, 7.3 Hz, 1H), 1.23 (d, J= 6.2 Hz, 3H).
  • 6
  • (S)-(benzyl(2-hydroxyethyl)amino)propan-2-ol [ No CAS ]
  • [ 1147108-99-3 ]
  • 7
  • (S)-2-methyl-4-(4-nitrobenzenesulfonyl)morpholine [ No CAS ]
  • [ 1147108-99-3 ]
YieldReaction ConditionsOperation in experiment
(c) (SV 2-methylmorpholine hydrochloride To a solution of (S)-2-methyl-4-(4-nitrobenzenesulfonyl)nnorpholine (1 g, 3.5 mmol) and Lithium hydroxide monohydrate (0.586 g, 13.97 mmol) in ACN (35 ml.) was added 1- propanthiol (1.26 ml_, 13.97 mmol) at RT and the resultant mixture stirred overnight. 1.25M HCI in MeOH (5 eq.) was added. The volatiles were removed under vacuum to give crude (S)-2-methylmorpholine hydrochloride. This solid residue was repeatedly washed with cyclohexane to remove apolar by-products, affording (S)-2-methylmorpholine hydrochloride (Intermediate B*) which was used in the next step without further purification. MS (+ve ion electrospray): m/z 102 [MH+]
  • 8
  • [ 1147108-99-3 ]
  • [ 2972-52-3 ]
  • (2,4-dichloropyrimidin-5-yl)[(S)(2-methylmorpholino)]methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 0℃; for 3h;Inert atmosphere; (a) (2^-dichloropyrimidin-5-ynr(5)(2-methylmorpholino')1methanone (compound 3* fcom pound 3, (S) enantiomeric Phosphorus pentachloride (1190 g, 5.70 mol, sinoreagent) was added portionwise to a suspension of 2,4-dihydroxypyrimidine-5-carboxylic acid (compound 1) (254 g, 1.6 mol, Shanghai Bide) in phosphorous oxychloride (2 Kg, 13.02 mol, Qingxian Keruixi) at 25 C. The reaction mixture was heated to 115 C and stirred for 16h. The reaction was cooled to 27C and the volatiles were removed under vacuum to provide a yellow semi-solid. Petroleum ether (700 mL) was added to the crude product where precipitation occurred. The mixture was filtered and the filter cake was washed with petroleumm ether (200 mL). The filtrate was evaporated under reduced pressure to give 2,4-dichloropyrimidine-5-carbonyl chloride (compound 2) as a yellow oil (268 g, 78% yield). This material was used in the next step without further purification. A solution of (S)-2-methylmorpholine (Intermediate B*) (141 g, 1.39 mol, Shanghai Shuya) and TEA (141.1 g, 1.4 mol, Tianjin Fuchen) in DCM (1000 mL) was added dropwise to a stirred solution of 2,4-dichloropyrimidine-5-carbonyl chloride (compound 2) (268 g, 1.3 mol) in dry DCM (3000 mL) at 0 C under N2. The reaction mixture was stirred for 3 h at 0 C and then quenched with H20 (500 mL). The phases were separated and the aqueous phase was extracted with DCM ( 2 x 300mL). The combined organic phases were washed with 0.5 M HCI (1000 mL), brine (2000 mL), dried over Na2S04 and then evaporated under reduced pressure. The residue was purified by flash column chromatography (petroleum/EtOAc 20/1 to 1/1) to give desired (2,4-dichloropyrimidin-5-yl)[(S)(2-methylmorpholino)]methanone (compound 3*) as a yellow oil (188 g, 53% yield). *H NMR (400 MHz, DMSO-d6) delta: 8.86 (1H, s), 4.33 - 4.25 (1H, m), 3.95 - 3.68 (1H, m), 3.58 - 3.37 (3H, m), 3.17 - 2.64 (2H, m), 1.20 - 0.98 (3H, m).
  • 9
  • 3,6-di-bromo-isothiazolo[4,3-b]pyridine [ No CAS ]
  • [ 1147108-99-3 ]
  • (S)-4-(6-bromoisothiazolo[4,3-b]pyridin-3-yl)-2-methylmorpholine [ No CAS ]
  • 10
  • C54H90N4O18 [ No CAS ]
  • [ 1147108-99-3 ]
  • [(2R,3S,4R,5R,7S,9S,10S,11R,12S,13R)-2-[(1S)-2-[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyltetrahydro-2H-pyran-2-yl]oxy-1-methylethyl]-10-[(2S,3R,4E,6R)-3-hydroxy-4-methoxyimino-6-methyltetrahydropyran-2-yl]oxy-3,5,7,9,11,13-hexamethyl-4-(3-methylbutanoyloxy)-6,14-dioxo-12-[[(2S,5R,7R)-2,4,5-trimethyl-1,4-oxazepan-7-yl]oxy]oxacyclotetradecan-7-yl] (2S)-2-methylmorpholine-4-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
0.36 g With 1-hydroxy-pyrrolidine-2,5-dione; triethylamine; In acetonitrile; at 70℃; for 20h; To a solution of intermediate E (0,4g, 369 muetaiotaomicronIota) and N-hydroxysuccinimide (0,13 g, 618,29 muetaiotaomicronIota) in CH3CN (8 ml) was added dropwise a solution of <strong>[1147108-99-3](2S)-2-methylmorpholine hydrochloride</strong> (0,107 g, 738 mupiiotaomicronIota) in CH3CN (4 ml) and TEA (155 muIota, 1 .1 1 mmol) at 70C. The resulting mixture was stirred at 70C for 20h. After cooling to room temperature, the reaction was diluted with EtOAc (10ml), washed with H20 (10 ml), brine (10 ml), dried over MgS04, filtered and the filtrate was concentrated under reduced pressure to afford 0.48 g of crude product as pale oil. The residue was purified by silica gel column (20 g SiOH 15- 40 muetaiota, EtOAc-NEt3 98/2) to afford 0.36 g of the expected product as a white solid. (0349) NMR 1 H (500MHz, delta in ppm , DMSO-d6): 0.78 (d, J=6.8 Hz, 3 H); 0.91 (m, 6 H); 0.96 (d, J=6.6 Hz, 6 H); 0.99 to 1 .14 (m, 21 H); 1 .65 to 2.06 (m, 12 H); 2.08 to 2.23 (m, 6 H); 2.39 (m, 2 H); 2.58 (m, 2 H); 2.65 to 2.95 (m, 7 H); 3.03 (m, 2 H); 3.28 to 3.40 (m, 4 H); 3.46 (s, 3 H); 3.52 (m, 1 H); 3.59 to 3.83 (m, 8 H); 3.90 (s large, 1 H); 4.19 (m, 1 H); 4.45 (d, J=7.9 Hz, 1 H); 4.63 (m, 3 H); 4.86 (d, J=7.1 Hz, 2 H); 5.17 to 5.39 (m, 1 H) MS method d: (0350) Retention time (0351) Tr (min): 1 .02 ; [M+H]+ 1 1 16 ; [M-H+HCOOH]-: m/z 1 160 (base peak)
0.36 g With 1-hydroxy-pyrrolidine-2,5-dione; triethylamine; In acetonitrile; at 70℃; for 20h; To a solution of intermediate E (0,4g, 369muetaiotaomicronIota) and N-hydroxysuccinimide (0,13 g, 618,29 muetaiotaomicronIota) in CH3CN (8 ml) was added dropwise a solution of <strong>[1147108-99-3](2S)-2-methylmorpholine hydrochloride</strong> (0,107 g, 738 mupiiotaomicronIota) in CH3CN (4 ml) and TEA (155 muIota, 1 .1 1 mmol) at 70C. The resulting mixture was stirred at 70C for 20h. After cooling to room temperature, the reaction was diluted with EtOAc (10ml), washed with H20 (10 ml), brine (10 ml), dried over MgS04, filtered and the filtrate was concentrated under reduced pressure to afford 0.48 g of crude product as pale oil. The residue was purified by silica gel column (20 g SiOH 15- 40 muetaiota, EtOAc- NEt3 98/2) to afford 0.36 g of the expected product as a white solid. (0333) 1 H NMR (500MHz, delta in ppm , DMSO-d6): (0334) 0.78 (d, J=6.8 Hz, 3 H); 0.91 (m, 6 H); 0.96 (d, J=6.6 Hz, 6 H); 0.99 to 1 .14 (m, 21 H); 1 .65 to 2.06 (m, 12 H); 2.08 to 2.23 (m, 6 H); 2.39 (m,2 H); 2.58 (m, 2 H); 2.65 to 2.95 (m, 7 H); 3.03 (m, 2 H); 3.28 to 3.40 (m, 4 H); 3.46 (s, 3 H); 3.52 (m, 1 H); 3.59 to 3.83 (m, 8 H); 3.90 (s large, 1 H); 4.19 (m, 1 H); 4.45 (d, J=7.9 Hz, 1 H); 4.63 (m, 3 H); 4.86 (d, J=7.1 Hz, 2 H); 5.17 to 5.39 (m, 1 H) (0335) MS method i: Retention time Tr (min): 1 .02 ; [M+H]+ 1 1 16 ; [M-H+HCOOH]-: m/z 1 160 (base peak)
  • 11
  • C54H85N3O21 [ No CAS ]
  • [ 1147108-99-3 ]
  • C56H92N2O22 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1-hydroxy-pyrrolidine-2,5-dione; In acetonitrile; at 70 - 80℃; for 12h; To a mixture of Intermediate G (5.00 g, 4.50 mmol, 1 .00 eq) and 1 -hydroxypyrrolidine- 2,5-dione (1 .18 g, 10.26 mmol, 2.28 eq) in CH3CN (40 mL) was added dropwise a solution of (2S)-2-methylmorpholine (910.35 mg, 9.00 mmol, 2.00 eq) in CH3CN (10 mL) at 70 C, then the resulting mixture was stirred at 80 C for 12 hour. LCMS showed the starting material was consumed and one new peak with desired product was detected. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove most of CH3CN. The residue was diluted with EtOAc (100 mL), then washed with H20 (50 mL x 3), brine (50 mLx3), dried over anhydrous Na2S04, filtered and the filtrate was concentrated under reduced pressure to give desired compound (5.00 g, crude) as a yellow solid. MS method e: (0373) Retention time Tr (min): 1 .29; m/z 1 167.9 [M+Na] +
  • 12
  • 5-chloro-2-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4-yl]methyl]pyridazin-3-one [ No CAS ]
  • [ 1147108-99-3 ]
  • 2-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4-yl]methyl]-5-[(2S)-2-methylmorpholin-4-yl]pyridazin-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
89% With potassium carbonate; In dimethyl sulfoxide; acetonitrile; at 70℃; for 18h; General procedure: To a stirred suspension of 5-chloro-2-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4- yl]methyl]pyridazin-3-one (building block A, 300 mg, 0.947 mmol) and (R)-3- hydroxypyrrolidine (0.14 mL, 1.73 mmol) in DMSO (0.5 mL) and acetonitrile (3 mL) was added potassium carbonate (393 mg, 2.84 mmol) Then the reaction mixture was stirred at 70 C for 18 h. After cooling to room temperature the reaction mixture was diluted with EtOAc (80 mL) was washed three times with water (10 mL) and brine (10 mL). The aqueous layers were back extracted twice with EtOAc (80 mL). The combined organic extracts were dried (Na2S04), filtered and concentrated in vacuo. Purification by flash chromatography (silica, gradient: 0% to 10% MeOH in CH2CI2) afforded the title compound (341 mg, 93 %) as an off-white foam. MS (ESI): 368.2 ([M+H]+).
  • 13
  • 5-chloro-2-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4-yl]methyl]pyridazin-3-one [ No CAS ]
  • [ 1147108-99-3 ]
  • 5-[(2S)-2-methylmorpholin-4-yl]-2-[[3-(6-methyl-3-pyridyl)isoxazol-4-yl]methyl]pyridazin- 3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With potassium carbonate; In dimethyl sulfoxide; acetonitrile; at 70℃; for 18h; General procedure: To a stirred suspension of 5-chloro-2-[[5-methyl-3-(6-methyl-3-pyridyl)isoxazol-4- yl]methyl]pyridazin-3-one (building block A, 300 mg, 0.947 mmol) and (R)-3- hydroxypyrrolidine (0.14 mL, 1.73 mmol) in DMSO (0.5 mL) and acetonitrile (3 mL) was added potassium carbonate (393 mg, 2.84 mmol) Then the reaction mixture was stirred at 70 C for 18 h. After cooling to room temperature the reaction mixture was diluted with EtOAc (80 mL) was washed three times with water (10 mL) and brine (10 mL). The aqueous layers were back extracted twice with EtOAc (80 mL). The combined organic extracts were dried (Na2S04), filtered and concentrated in vacuo. Purification by flash chromatography (silica, gradient: 0% to 10% MeOH in CH2CI2) afforded the title compound (341 mg, 93 %) as an off-white foam. MS (ESI): 368.2 ([M+H]+).
  • 14
  • [ 1147108-99-3 ]
  • [ 79-08-3 ]
  • (S)-2-(2-methylmorpholino)acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
88.2% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; General procedure: To a stirred solution of (R)-2-methylmorpholine hydrochloride (A2, 0.2 g, 1.45 mmol) and K2CO3(0.8 g, 5.79 mmol) in anhydrous DMF (1.5 mL) was added bromoacetic acid (0.23 g, 1.67 mmol) dissolved in 2 mL anhydrous DMF under the protection of argon. The reaction mixture was stirred at room temperature overnight. Water (5mL) was added to the reaction solution, and the suspension was filtered through Celite 545 . The filtrate was extracted with dichloromethane (35 mL). The aqueous phase was cooled in an ice bath and neutralized with 4 M HCl to pH 3.0 without solid precipitation. The solvent was removed under reduced pressure. The obtained solid was dissolved with 1 mL methanol and filtered. The filtrate was concentrated under reduced pressure to obtain colorless oil (B2). The yield was 87.0 % (0.2 g).
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