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[ CAS No. 1339058-28-4 ] {[proInfo.proName]}

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Chemical Structure| 1339058-28-4
Chemical Structure| 1339058-28-4
Structure of 1339058-28-4 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1339058-28-4 ]

CAS No. :1339058-28-4 MDL No. :MFCD16866649
Formula : C12H12N2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :ZLQJFZUDUHSAHM-UHFFFAOYSA-N
M.W : 216.24 Pubchem ID :62748662
Synonyms :

Calculated chemistry of [ 1339058-28-4 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.17
Num. rotatable bonds : 3
Num. H-bond acceptors : 4.0
Num. H-bond donors : 1.0
Molar Refractivity : 60.09
TPSA : 55.24 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.92 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.9
Log Po/w (XLOGP3) : 0.99
Log Po/w (WLOGP) : 1.49
Log Po/w (MLOGP) : 0.7
Log Po/w (SILICOS-IT) : 2.3
Consensus Log Po/w : 1.48

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.16
Solubility : 1.49 mg/ml ; 0.0069 mol/l
Class : Soluble
Log S (Ali) : -1.74
Solubility : 3.95 mg/ml ; 0.0183 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -4.13
Solubility : 0.0159 mg/ml ; 0.0000735 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.07

Safety of [ 1339058-28-4 ]

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 [ 1339058-28-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1339058-28-4 ]

[ 1339058-28-4 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 1799639-94-3 ]
  • [ 1339058-28-4 ]
  • [ 1799639-24-9 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 0 - 60℃; for 2h; 843 Example 843 ethyl (2R)-2- { [(5Sa)5(3 -ehloro-4-methoxy-2-methylphenyl)-6-(4- fluorophenyl)thieno [2,3 -djpyrimidin-4-yl joxy} -3 -(2- { [2-(2-methoxyphenyl)pyrirnidin-4- yl}rnethoxy}phenyl)propanoate 1.40 g (2.36 mmol) Preparation 81, 1.55 g (5.90 mmol) PPh3, 1.27 g (5.90 mmol)Preparation 9bp and 20 ml toluene were cooled to 0 °C and 1.36 g (5.90 mmol) di-tertbutyl azodicarboxylate was added. Mixture was stirred at 60 °C for 2hs. Mixture was then concentrated and purified via flash chromatography using heptane-EtOAc-MeOH as eluents to obtain Example 843. HRMS calculated for C43H36C1FN406 S: 790.2028, found:791.2123 (M+H).
  • 2
  • [ 1799639-97-6 ]
  • [ 1339058-28-4 ]
  • [ 1799638-82-6 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere; 795 Example 795 ethyl (2R)-2- { [(5S)-5- { 3 -chloro-2-methyl-4- [2-(piperazin- 1-yl)ethoxy]phenyl } -6-(4-fluorophenyl)thieno [2,3 -d]pyrimidin-4-yl] oxy} -3 -(2- { [2-(2- methoxyphenyl)pyrimidin-4-yllmethoxy }phenyl)propanoate 657 mg (0.95 mmol) ethyl (2R)-2- [(58a)-[3 -ehloro-2-methyl-4- [2-(piperazin- I -yl)ethoxy]phenyl] -6-(4-fluorophcnyl)thieno [2,3 -d]pyrimidin-4-yl]oxy-3 -(2-hydroxyphenyl) propanoate (Preparation 8o), 411 mg (1.9 mnrnl) 2-[2-(2-methoxyphcnyl)pyrimidin-4-yIj methanol (Preparation 9bp) and 498 ing (1.9 mmol) triphenyl phosphine were dissolved in 25 ml abs. toluene, then 437 mg (1.9 mmol) ditertbutyl azodicarboxylate was added. The mixture was stin’ed at 50°C under nitrogen until no further conversion was observed.The volatiles were evaporated under reduced pressure and the crude intermediate was purified via flash chromatography using ethyl acetate and methanol as eluents to obtain Example 795. HRMS calculated for C45H46C1FN6O6S: 888.2872; found 445.1502
  • 3
  • [ 1339465-55-2 ]
  • [ 1339058-28-4 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; potassium carbonate at 0℃; for 0.5h; 9bp.B 261 mg 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine (1.00 mmol) was dissolved in 2 rnL HCI in dioxane (4M solution), then 2 mL water was added and this mixture was stirred at 50 °C for 16h. The reaction mixture was cooled to 0°C, then 320 mg NaOH (8.0nimol) was added portionwise. The p11 was adjusted to 8 using 10% K2C03 solution, then76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for 30 mm at 0°C. The reaction mixture was diluted with 5 mL water and extracted with EtOAc. The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane andEtOAc as eluents to give the title product.‘H NMR (400 MHz, DMSO-d6): 8.84 (d, lET), 7.50-7.42 (m, 3H), 7.14 (d, 111), 7.03 (m, 111), 5.66 (t, 111), 4.58 (d, 211), 3.75 (s, 311).
  • 4
  • [ 67751-23-9 ]
  • 2-methoxybenzamidine acetic acid salt [ No CAS ]
  • [2-(2-methoxyphenyl)pyrimidin-4-yl]methanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium methylate; In methanol; at 75℃; for 2h; General procedure: To the mixture of the appropriate amidine hydrochloride (1.2 eq.) and (E)-4- (dimethylamino)-1,1-dimethoxy-but-3-en-2-one (Preparation 9a1, 1.0 eq.) in dry methanol (0.5 mL/mmol) sodium inethoxide (1.2 eq.) was added portionwise and the mixture was stirred at 75 C for 2 h. The reaction mixture was cooled and concentratedunder reduced pressure. To the residue water was added and it was extracted with DCM. The combined organic layers were dried over MgSO4, fihered and concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAe as eluents. Starting from 2-methoxybenzamidine acetic acid salt using General Procedure 9C 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine was obtained.111 NMR (400 MHz, DMSO-d6): 8.93 (d, 111), 7.55-7.44 (m, 311), 7.16 (d, lI-I), 7.06 (in,111), 5.31 (s, 111), 3.76 (s, 311), 3.37 (s, 611).
  • 5
  • [ 1799849-72-1 ]
  • [ 1339058-28-4 ]
  • [ 1799637-47-0 ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); copper(I) thiophene-2-carboxylate In tetrahydrofuran at 70℃; Inert atmosphere; (2R)-2- { [(5R0)-5- { 3 -chloro-2-methyl-4-[2-(4-methylpiperazin-yl)cthoxylphcnyl } -6-(4-fluorophcnyl)thicno[2,3 -a]pyrimidin-4-yljoxy} -3 -(2- { [2-(2- methoxyphenyl)pyrimidin-4-yl]rnethoxy}phenyl)propanoic acid I eq. ethyl (2R)-2- ft5R)-5 -[3 -ehloro-2-methyl-4- [2-(4-methylpiperazin- 1 -yl)ethoxyj phenyl] -6-(4-fiuorophenyl)thieno [2,3 -d]pyrimidin-4-yl] oxy-3 - [2-[(2-methylsulfanylpyrhnidin-4-yl)methoxy] phenyljpropanoate (Preparation 11k), 3.0 eq. [2-(2-methoxy phenyl)pyrirnidin-4-yl]methanol (Preparation 9hp) and 3.0 eq. copper(1)thiophenecarboxylate were dissolved in dry THF (0.1 M for Preparation l0e), then 0.15 eq. Pd(PPh3)4 was added. The mixture was stilTed at 70°C under nitrogen until no Thither conversion was observed. Then it was concentrated under reduced pressure and the crude intermediate was purified via flash chromatography using diehloromethane and methanol as eluents. The obtained intermediate was dissolved in dioxane-water 1:1 (10 mL/mmol)and 10 eq LiOll x 1120 was added. The mixture was stirred at room temperature until no further conversion was observed. Then it was diluted with brine, neutralized with 2 M MCI, extracted with DCM. The combined organic phases were dried over Na2804, filtered and concentrated under reduced pressure and purified via preparative reversed phase chromatography using 5 mM aqueous NH4HCO3 solution and MeCN as eluents to obtainExample 826. HRIvIS calculated for C47H44C1FN606S: 874.2716; found 438.1443 (M+211).
  • 6
  • [ 1548269-17-5 ]
  • [ 1339058-28-4 ]
YieldReaction ConditionsOperation in experiment
87% With hydrogenchloride In water at 60℃;
Multi-step reaction with 2 steps 1: hydrogenchloride / 1,4-dioxane / 16 h / 50 °C 2: potassium carbonate; sodium tetrahydroborate / 0.5 h / 0 °C / pH 8
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride In 1,4-dioxane; water at 50℃; for 16h; Stage #2: With sodium tetrahydroborate; sodium hydroxide In 1,4-dioxane; water at 0℃; for 0.5h; 11.B Step B: Preparation 11 261 mg 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine (1.0 mmol) was dissolved in 2 mL HC1 in dioxane (4M solution), then 2 mL water was added and this mixture was stirred at 50 °C for 16 hours. The reaction mixture was cooled to 0 °C, then 320 mg NaOH (8.0 mmol) was added portionwise. The pH was adjusted to 8 using 10 % K2CO3 solution, then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for 30 minutes at 0 °C. The reaction mixture was diluted with 5 mL water and extracted with EtOAc. The combined organic phases were dried over Na2S04 and concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to give Preparation 11. 1H NMR (400 MHz, DMSO-d6): 8.84 (d, 1H), 7.50-7.42 (m, 3H), 7.14 (d, 1H), 7.03 (m, 1H), 5.66 (t, 1H), 4.58 (d, 2H), 3.75 (s, 3H)
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride; water In 1,4-dioxane at 50℃; for 16h; Stage #2: With sodium tetrahydroborate In 1,4-dioxane at 0℃; for 0.5h; C3.B Step B: Preparation C3 261 mg 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine (1.0 mmol) was dissolved in 2 mL HC1 in dioxane (4M solution), then 2 mL water was added and this mixture wasstirred at 50 °C for 16 hours. The reaction mixture was cooled to 0 °C, then 320 mg NaOH (8.0 mmol) was added portionwise. The pH was adjusted to 8 using 10 % K2C03 solution,then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for 30 minutes at 0 °C. The reaction mixture was diluted with 5 mL water and extracted with EtOAc. The combined organic phases were dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flashchromatography using heptane and EtOAc as eluents to give Preparation C3. 1H NMR(400 MHz, DMSO-d6) ö: 8.84 (d, 1H), 7.50-7.42 (m, 3H), 7.14 (d, 1H), 7.03 (m, 1H), 5.66 (t, 1H), 4.58 (d, 2H), 3.75 (s, 3H)
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride In 1,4-dioxane; water at 50℃; for 16h; Stage #2: With sodium tetrahydroborate In 1,4-dioxane; water at 0℃; for 0.5h; 5b.B Preparation 5b 261 mg 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine (1.0 mmol) was dissolved in 2 mL HC1 in dioxane (4M solution), then 2 mL water was added and this mixture was stirred at 50 °C for 16 hours. The reaction mixture was cooled to 0 °C, then 320 mg NaOH (8.0 mmol) was added portionwise. The pH was adjusted to 8 using 10 % aqueous K2C03 solution, then 76 mg sodium boro hydride (2.0 mmol) was added and the mixture was stirred for 30 minutes at 0 °C. The reaction mixture was diluted with 5 mL water and extracted with EtOAc. The combined organic phases were dried over Na2S04, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and EtOAc as eluents to give Preparation 5b. 1H NMR (400 MHz, DMSO-d6) δ: 8.84 (d, 1H), 7.50-7.42 (m, 3H), 7.14 (d, 1H), 7.03 (m, 1H), 5.66 (t, 1H), 4.58 (d, 2H), 3.75 (s, 3H)
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride In 1,4-dioxane at 50℃; for 16h; Stage #2: With sodium tetrahydroborate; water In 1,4-dioxane at 0℃; for 0.5h; 8.O Step O: [2-(2-Methoxyphenyl)pyrimidin-4-yl]methanol Step O: [2-(2-Methoxyphenyl)pyrimidin-4-yl]methanol (0196) 261 mg compound of Step N above (1.0 mmol) was dissolved in 2 mL 4M HC1 solution (in dioxane), then 2 mL water was added and this mixture was stirred at 50 °C for 16 hours. The reaction mixture was cooled to 0 °C, then 320 mg NaOH (8.0 mmol) was added portionwise. The pH was adjusted to 8 using 10 % K2C03 solution, then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for 30 minutes at 0 °C. The reaction mixture was diluted with 5 mL water and extracted with ethyl acetate. The combined organic phases were dried over Na2S04, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via flash chromatography using heptane and ethyl acetate as eluents to give [2-(2- methoxyphenyl)pyrimidin-4-yl]methanol. 'H NMR ^OO MHZ, DMSO-d6) δ: 8.84 (d, 1H), 7.50-7.42 (m, 3H), 7.14 (d, 1H), 7.03 (m, 1H), 5.66 (t, 1H), 4.58 (d, 2H), 3.75 (s, 3H)
With hydrogenchloride In 1,4-dioxane; water at 50℃; for 14h; 4.4F (2-(2-methoxyphenyl)pyrimidin-4-yl)methanol A mixture of Example 4E (14.7 g) in 1 10 mL HC1 in dioxane (4M mixture) and 1 10 mL water was heated at 50 °C for 14 hours. The mixture was cooled to 0 °C, and ground NaOH (17.60 g) was added in portions. The pH was adjusted to 8 using 10% K2CO3 aqueous mixture. NaBH4 (4.27 g) was added in portions. The mixture was stirred at 0 °C for 45 minutes. The mixture was carefully quenched with 150 mL saturated aqueous NH4C1 and was stirred at 0 °C for 30 minutes. The mixture was extracted with ethyl acetate (5 x 150 mL), washed with brine, dried over MgSC>4, filtered, and concentrated. The residue was triturated in 30 mL ethanol to give a first crop of the title compound. The filtrate was concentrated and the residue was purified on a silica gel column (120 g, 55-100% ethyl acetate in heptanes, dry load) to give a second crop of the title compound. NMR (500 MHz, DMSO-cfe) δ ppm 8.84 (d, IH), 7.49 (m, 2H), 7.44 (ddd, IH), 7.13 (dd, IH), 7.04 (td, IH), 5.65 (t, IH), 4.60 (dd, 2H), 3.75 (s, 3H). MS (DCI) m/z 217.0 (M+H)+.
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride; water In 1,4-dioxane at 50℃; for 14h; Stage #2: With sodium tetrahydroborate; potassium carbonate; sodium hydroxide In 1,4-dioxane; water at 0℃; for 0.75h; 1.1G (2-(2-methoxyphenyl)pyrimidin-4-yl)methanol Example 1G (2-(2-methoxyphenyl)pyrimidin-4-yl)methanol A mixture of Example 1F (14.7 g) in 110 mL HCl in dioxane (4M mixture) and 110 mL water was heated at 50° C. for 14 hours. The mixture was cooled to 0° C., and ground NaOH (17.60 g) was added in portions. The pH was adjusted to 8 using 10% K2CO3 aqueous mixture. NaBH4 (4.27 g) was added in portions. The mixture was stirred at 0° C. for 45 minutes. The mixture was carefully quenched with 150 mL saturated aqueous NH4Cl and was stirred at 0° C. for 30 minutes. The mixture was extracted with ethyl acetate (5*150 mL), washed with brine, dried over MgSO4, filtered, and concentrated. The residue was triturated in 30 mL ethanol to give a first crop of the title compound. The filtrate was concentrated and the residue was purified on a silica gel column (120 g, 55-100% ethyl acetate in heptanes, dry load) to give a second crop of the title compound. 1H NMR (500 MHz, dimethyl sulfoxide-d6) δ ppm 8.84 (d, 1H), 7.49 (m, 2H), 7.44 (ddd, 1H), 7.13 (dd, 1H), 7.04 (td, 1H), 5.65 (t, 1H), 4.60 (dd, 2H), 3.75 (s, 3H). MS (DCI) m/z 217.0 (M+H)+.
Stage #1: 4-(dimethoxymethyl)-2-(2-methoxyphenyl)pyrimidine With hydrogenchloride In 1,4-dioxane; water at 50℃; for 14h; Stage #2: With sodium tetrahydroborate; water In 1,4-dioxane at 0℃; for 0.75h; 18E Example 18E(2-(2-methoxypheny l)pyrimidin-4-yl)methanol A mixture of Example l8D (14.7 g) in 110 mL HCI in dioxane (4M mixture) and 110 mL water was heated at 50 °C for 14 hours. The mixture was cooled to 0 °C, and ground NaOl-I (17.60 g) was added in portions. The pH was adjusted to 8 using 10% K2C03 aqueous mixture. Sodium borohydride (4.27 g) was added in portions. The mixture was stirred at 0 °C for 45 minutes. The mixture wascarefully quenched with 150 mL saturated aqueous NH4CI and was stirred at 0 °C for 30 minutes. The mixture was extracted with ethyl acetate (5 x 150 mL), washed with brine, dried over MgSO4, filtered, and concentrated. The residue was triturated in 30 mL ethanol to give a first crop of the title compound. The filtrate was concentrated and the residue was purified on a silica gel column (120 g, 55-100% ethyl acetate in heptanes, dry load) to give a second crop of the title compound. ‘H NMR (500 MHz,dimethylsulfoxide-d6) 6 ppm 8.84 (d, 1H), 7.49 (m, 2H), 7.44 (ddd, IH), 7.13 (dd, IH), 7.04 (td, IH),5.65 (t, IH), 4.60 (dd, 2H), 3.75 (s, 3H). MS (DCI) m/z 217.0 (M+H).

  • 7
  • [ 1339058-28-4 ]
  • [ 1799611-75-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triphenylphosphine; di-tert-butyl-diazodicarboxylate / toluene / 50 °C / Inert atmosphere 2: sodium hydroxide; water / tetrahydrofuran / 20 °C 3: sulfuric acid / water / 60 °C
Multi-step reaction with 2 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 50 °C / Inert atmosphere 1.2: 20 °C 2.1: sulfuric acid / 60 °C
Multi-step reaction with 2 steps 1.1: triphenylphosphine; diethylazodicarboxylate / toluene / 50 °C / Inert atmosphere 1.2: 50 °C 2.1: sulfuric acid / 60 °C
  • 8
  • [ 1339058-28-4 ]
  • [ 1799611-07-6 ]
  • [ 2756361-11-0 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere; 3br (2R)-2-Llydroxy-3- [2-j j2-(2-methoxyphenyl)pyrinfldin-4-ylj methoxy]phenyl] propanoic acid 37.84 g (150 mrnol) ethyl (2R)-2-acetoxy-3-(2-hydroxyphenyl)propanoate (Preparation3aa-(R)), 48.65 g (225 mmol) [2-(2-rnethoxyphenyl)pyrirnidin-4-yl]methanol(Preparation 9bp) and 59.01 g (225 mmol) triphenyl phosphine were dissolved in 160 mL abs. toluene, then 102.47 mL (225 mmol) diethylazodiearboxylate was added. The mixture was stirred at 50°C under nitrogen until no further conversion was observed. The volatiles were evaporated under reduced pressure. Then 400 mL Et20 was added, the mixture was sonicated and filtered (to remove PPh3). lEt2O was removed in vaeuo. Residue wasdissolved in 130 mL TIIF, then 30 g NaOH in 130 mL 1420 was added. The mixture was stirred at room temperature until no further conversion was observed. Then it was acidified with 2 M HCI, THF was removed in vacou. 300 mL diehioromethane was added, and the precipitate was filtered, washed with cold 1420 and DCM dried in vaeuo to obtain Preparation 3br.11-NMR (400 MHz, DMSO-d6): 8.88 (d, 111), 7.80 (d, 1H), 7.55 (dd, 1H), 7.49-7-44 (ni,111), 7.26 (dd, IH), 7.17-7.11 (m, 2H), 7.06 (t, 1H), 6.98 (d, 111), 6.88 (t, 1H), 5.22 (s, 2H),3.81 (dd, 111), 3.77 (s, 311), 3.73 (dd, 1H), 2.44 (dd, lH).
  • 9
  • [ 1339058-28-4 ]
  • [ 1799611-07-6 ]
  • [ 1799611-74-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: [2-(2-methoxyphenyl)pyrimidin-4-yl]methanol; ethyl (2R)-2-acetoxy-3-(2-hydroxyphenyl)propanoate With triphenylphosphine; diethylazodicarboxylate In toluene at 50℃; Inert atmosphere; Stage #2: With water; sodium hydroxide In tetrahydrofuran at 20℃; 13.Q Step Q: (2R)-2-Hydroxy-3-[2-[[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl] propanoic acid 37.84 g (150 mmol) Preparation 3, 48.65 g (225 mmol) [2-(2-methoxyphenyl)pyrimidin- 4-yl]methanol and 59.01 g (225 mmol) triphenyl phosphine were dissolved in 160 mL absolute toluene, then 102.47 mL (225 mmol) diethylazodicarboxylate was added. The mixture was stirred at 50 °C under nitrogen until no further conversion was observed. The volatiles were evaporated under reduced pressure. Then 400 mL Et20 was added, the mixture was sonicated and filtered (to remove PPh3). Et20 was removed in vacuo. Residue was dissolved in 130 mL THF, then 30 g NaOH in 130 mL H20 was added. The mixture was stirred at r.t. until no further conversion was observed. Then it was acidified with 2 M HC1, THF was removed in vacuo. 300 mL DCM was added, and the precipitate was filtered, washed with cold H20 and DCM dried in vacuo to obtain(2i?)-2-hydroxy-3-[2-[[2- (2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl]propanoic acid. 1H-NMR (400 MHz, DMSO-de): 8.88 (d, 1H), 7.80 (d, 1H), 7.55 (dd, 1H), 7.49-7-44 (m, 1H), 7.26 (dd, 1H), 7.17-7.11 (m, 2H), 7.06 (t, 1H), 6.98 (d, 1H), 6.88 (t, 1H), 5.22 (s, 2H), 3.81 (dd, 1H), 3.77 (s, 3H), 3.73 (dd, 1H), 2.44 (dd, 1H)
Stage #1: [2-(2-methoxyphenyl)pyrimidin-4-yl]methanol; ethyl (2R)-2-acetoxy-3-(2-hydroxyphenyl)propanoate With triphenylphosphine; diethylazodicarboxylate In toluene at 50℃; Inert atmosphere; Stage #2: With water; sodium hydroxide In tetrahydrofuran at 50℃; 2c.A (2R)-2-hydroxy-3-[2-[[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl] propanoic acid 30.3 g Preparation 2a (120 mmol), 38.9 g Preparation 5b (180 mmol) and 47.2 g triphenyl phosphine (180 mmol) were dissolved in 120 mL dry toluene, then 82 mL DEAD (180 mmol, 40 % in toluene) was added. The mixture was stirred at 50 °C under nitrogen atmosphere until no further conversion was observed. The volatiles were evaporated under reduced pressure. Then 300 mL DEE was added, the mixture was sonicated and filtered, washed with DEE. The filtrate was concentrated under reduced pressure. The residue was dissolved in 125 mL THF, then 24 g NaOH (0.6 mol) dissolved in 125 mL water was added. The mixture was stirred at 50 °C until no further conversion was observed. The pH was set to 5 with cc. HC1, and the volatiles were removed under reduced pressure. 100 mL water and 350 mL DCM were added, the mixture was stirred at 0 °C and the precipitate was filtered, washed with cold water and DCM and dried under reduced pressure to obtain (2i?)-2-hydroxy-3 - [2- [ [2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl]propanoic acid. 1H-NMR (400 MHz, DMSO-d6) δ: 8.88 (d, 1H), 7.80 (d, 1H), 7.55 (dd, 1H), 7.49- 7.44 (m, 1H), 7.26 (dd, 1H), 7.17-7.11 (m, 2H), 7.06 (t, 1H), 6.98 (d, 1H), 6.88 (t, 1H), 5.22 (s, 2H), 4.50 (d, 1H), 3.81 (dd, 1H), 3.77 (s, 3H), 3.73 (dd, 1H), 2.44 (dd, 1H)
  • 10
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere; 12.A Step A 1 eq. Preparation 9, 2 eq. of Preparation 11 and 2 eq. triphenyl phosphine were dissolved in absolute toluene (0.2M for the phenol), then 2 eq. di-tert-butyl azodicarboxylate was added. The mixture was stirred at 50 °C under nitrogen until no further conversion was observed. The volatiles were evaporated under reduced pressure and the crude intermediate was purified via flash chromatography using ethyl acetate and methanol as eluents
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere;
  • 11
  • [ 1339058-28-4 ]
  • [ 2058055-22-2 ]
  • [ 2095238-40-5 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 60℃; Inert atmosphere; 8-9.C ethyl (2R)-2-[[5-bromo-6-(4-fluorophenyl)furo[2,3-d]pyrimidin-4-yl]amino]-3-[2-[[2-(2-methoxyphenyl)pyrimidin-5-yl]methoxy]phenyl]propanoate 500 mg ethyl (2i?)-2-[[5-bromo-6-(4-f uorophenyl)furo[2,3-3 (2.5 mmol) were dissolved in 20 mL dry toluene under N2 atmosphere, then 576 mg DTAD (2.5 mmol) was added. The mixture was stirred at 60 °C until no further conversion was observed. The mixture was then concentrated under reduced pressure and purified via flash chromatography using heptane and EtOAc as eluents to give ethyl (2i?)-2-[[5-bromo- 6-(4-fluorophenyl)furo [2,3 - ]pyrimidin-4-yl] amino]-3 - [2- [ [2-(2-methoxyphenyl) pyrimidin-5-yl]methoxy]phenyl]propanoate. HRMS (M+H)+: 698.1402
  • 12
  • [ 1339058-28-4 ]
  • [ 2058054-94-5 ]
  • [ 2058054-95-6 ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 35 - 45℃; 2i.B ethyl (2R)-2-amino-3-[2-[[2-(2-methoxyphenyl)pyrimidin-4-yl]methoxy]phenyl]propanoate 3.96 g ethyl (2i?)-2-amino-3-(2-hydroxyphenyl)propanoate hydrochloride (18.9 mmol) was dissolved in 200 mL dry toluene, then 5.69 g PPh3 (21.7 mmol), 4.69 g Preparation 5b (21.7 mmol) were added and the mixture was heated to 35 °C, then 5.0 g DTAD (21.7 mmol) was added and the mixture was stirred at 45 °C until no further conversion was observed. Then the mixture was concentrated under reduced pressure and purified via flash chromatography using EtOAc and MeOH as eluents. 1H NMR (500 MHz, DMSO-d6) δ: 8.92 (d, 1H), 7.61 (d, 1H), 7.55 (dd, 1H), 7.46 (td, 1H), 7.20 (td, 1H), 7.17 (dd, 1H), 7.15 (dd, 1H), 7.06 (td, 1H), 7.04 (dd, 1H), 6.91 (td, 1H), 5.27/5.23 (d, 2H), 4.01 (q, 2H), 3.76 (s, 3H), 3.68 (dd, 1H), 3.08 (br, 2H), 3.03/2.83 (dd, 2H), 1.07 (t, 3H) HRMS calculated for C23H25N304: 407.1845; found: 408.1928 (M+H)
  • 13
  • [ 1339058-28-4 ]
  • [ 2057523-16-5 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere; 8.P Step P: N-[(5S^-5-{3-Chloro-2-methyl-4-[2-(4-methylpiperazin-l-yl)ethoxy]phenyl}-6-(4- fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]-2-[2-(2-methoxyphenyl)pyrimidm^ (0198) ylJmethoxy}-D-phenylalanine (0199) 1 eq. of compound of Step L above, 2 eq. of compound of Step O above, and 3 eq. triphenylphosphine were dissolved in dry toluene (7 mL/mmol) under nitrogen atmosphere, then 3 eq. di-tert-butyl azodicarboxylate was added at room temperature. Then the mixture was stirred at 50 °C until no further conversion was observed. The volatiles were removed in vacuo and the residue was purified via flash chromatography using heptane and ethyl acetate as eluents. (0200) 1 eq. of the formed ester derivative was dissolved in tetrahydrofuran (15 mL/mmol) then 10 eq. lithium hydroxide monohydrate and water (15 mL/mmol) were added. The mixture was stirred at room temperature until no further conversion was observed. The pH was adjusted to 6 with 1M HC1 solution, then the mixture was diluted with brine, extracted with dichloromethane. The organic layer was dried over Na2S04, filtered and the filtrate was concentrated under reduced pressure. The crude product was purified via preparative reversed phase chromatography using 25 mM aqueous NH4HC03 solution and acetonitrile as eluents to yield N-[(55'iJ)-5-{3-chloro-2-methyl-4-[2-(4-methylpiperazin-l-yl)ethoxy] phenyl} -6-(4-fluorophenyl)thieno[2,3-(i]pyrimidin-4-yl]-2-[2-(2-methoxyphenyl) pyrimidin-4-yl]methoxy}-Z)-phenylalanine. HRMS calculated for C47H45CIFN7O5S: 873.2875, found: 437.6498 (M+2H)
With di-tert-butyl-diazodicarboxylate; triphenylphosphine In toluene at 50℃; Inert atmosphere;
  • 14
  • [ 1339058-28-4 ]
  • [ 2280986-86-7 ]
  • [ 2280986-95-8 ]
YieldReaction ConditionsOperation in experiment
With diamide; triphenylphosphine In tetrahydrofuran at 20℃; for 48h; Cooling with ice; 4.4G (R)-ethyl 2-acetoxy-3-(5-((tert-butyldimethylsilyl)oxy)-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate To an oven dried 500 mL round bottom flask was added Example ID (8 g), triphenylphosphine (13.71 g), Example 4F (6.78 g) and tetrahydrofuran (105 mL). The reaction flask was cooled in an ice bath. Solid (^-N^^V'^/V'-tetramethyldiazene-l ^-dicarboxamide (9 g) was added, and the reaction mixture was allowed to warm up to ambient temperature and was stirred overnight. After 48 hours, thin- layer chromatography indicated complete consumption of starting material. The reaction mixture was concentrated. Ethyl acetate (50 mL) was added, and the mixture was stirred for about 30 minutes and filtered. The filtrate was concentrated and purified by silica gel chromatography on a Grace Reveleris system using a 120 g silica column with 0-25% ethyl acetate/heptanes. Fractions containing the title compound were combined and concentrated to obtain the title compound. 'H NMR (400 MHz, DMSO- d6) 8 ppm 8.92 (d, IH), 7.59-7.50 (m, 2H), 7.46 (ddd, IH), 7.15 (dd, IH), 7.05 (td, I H), 6.95 (d, IH), 6.77-6.68 (m, 2H), 5.25-5.1 1 (m, 3H), 4.07 (qd, 2H), 3.76 (s, 3H), 3.26 (dd, 2H), 3.05 (dd, IH), 1.99 (s, 3H), 1.10 (t, 3H), 0.93 (s, 9H), 0.15 (s, 6H). MS (ESI) m/z 581.4 (M+H)+.
With diamide; triphenylphosphine In tetrahydrofuran at 20℃; for 48h; Cooling with ice; 68.68A (R)-ethyl 2-acetoxy-3-(5-((tert-butyldimethylsilyl)oxy)-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate Example 68A (R)-ethyl 2-acetoxy-3-(5-((tert-butyldimethylsilyl)oxy)-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate To an oven dried 500 mL round bottom flask was added Example 16D (8 g), triphenylphosphine (13.71 g), Example 1G (6.78 g) and tetrahydrofuran (105 mL). The reaction flask was cooled in an ice bath. Solid (E)-N,N,N',N'-tetramethyldiazene-1,2-dicarboxamide (9 g) was added and the reaction mixture was allowed to warm up to ambient temperature and was stirred overnight. After -2 minutes, a precipitate was observed. After 48 hours, thin-layer chromatography indicated complete consumption of starting material. The reaction mixture was concentrated. Ethyl acetate (50 mL) was added to the material and the mixture was stirred for about 30 minutes and filtered. The filtrate was concentrated and purified by silica gel chromatography on a Grace Reveleris system using a 120 g silica column with 0-25% ethyl acetate/heptanes. Fractions containing desired product were combined and concentrated to obtain the title compound. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 8.92 (d, 1H), 7.59-7.50 (m, 2H), 7.46 (ddd, 1H), 7.15 (dd, 1H), 7.05 (td, 1H), 6.95 (d, 1H), 6.77-6.68 (m, 2H), 5.25-5.11 (m, 3H), 4.07 (qd, 2H), 3.76 (s, 3H), 3.26 (dd, 2H), 3.05 (dd, 1H), 1.99 (s, 3H), 1.10 (t, 3H), 0.93 (s, 9H), 0.15 (s, 6H). MS (ESI) m/z 581.4 (M+H)+.
  • 15
  • [ 1339058-28-4 ]
  • [ 2280986-96-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: potassium carbonate / ethanol / 1 h / 20 °C
Multi-step reaction with 2 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: potassium carbonate / ethanol / 1 h / 20 °C
  • 16
  • [ 1339058-28-4 ]
  • [ 2280986-97-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: potassium carbonate / ethanol / 1 h / 20 °C 3: caesium carbonate / <i>tert</i>-butyl alcohol / 5 h / 65 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: potassium carbonate / ethanol / 1 h / 20 °C 3: caesium carbonate / <i>tert</i>-butyl alcohol / 5 h / 65 °C / Inert atmosphere
  • 17
  • [ 1339058-28-4 ]
  • [ 2283378-58-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.17 h
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.17 h
  • 18
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere 8.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran 9.1: lithium hydroxide monohydrate / tetrahydrofuran
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere 8.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran 9.1: lithium hydroxide monohydrate / tetrahydrofuran
  • 19
  • [ 1339058-28-4 ]
  • [ 2283378-64-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C
Multi-step reaction with 5 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C
  • 20
  • [ 1339058-28-4 ]
  • [ 2283378-66-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran
  • 21
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere
  • 22
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4: sodium ethanolate / ethanol / 3 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7: trifluoroacetic acid; water / dichloromethane / 20 °C
Multi-step reaction with 7 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3: hydrogen; acetic acid / water / 20 °C 4: sodium ethanolate / ethanol / 3 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7: trifluoroacetic acid; water / dichloromethane / 20 °C
  • 23
  • [ 1339058-28-4 ]
  • [ 2283377-35-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 11 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.1: magnesium sulfate / dichloromethane / 1 h / 20 °C 10.2: 1 h 11.1: lithium hydroxide monohydrate / tetrahydrofuran; methanol / 4 h
Multi-step reaction with 11 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.1: magnesium sulfate / dichloromethane / 1 h / 20 °C 10.2: 1 h 11.1: lithium hydroxide monohydrate / tetrahydrofuran; methanol / 4 h
  • 24
  • [ 1339058-28-4 ]
  • [ 2283377-55-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C
  • 25
  • [ 1339058-28-4 ]
  • [ 2283377-56-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere
  • 26
  • [ 1339058-28-4 ]
  • [ 2283379-51-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C
Multi-step reaction with 3 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3: toluene-4-sulfonic acid / dichloromethane / 20 °C
  • 27
  • [ 1339058-28-4 ]
  • [ 2283379-52-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 4.1: sodium ethanolate / ethanol / 1.5 h / 20 °C
Multi-step reaction with 4 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3: toluene-4-sulfonic acid / dichloromethane / 20 °C 4: sodium ethanolate / ethanol / 1.5 h / 20 °C
  • 28
  • [ 1339058-28-4 ]
  • [ 2283379-53-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 4.1: sodium ethanolate / ethanol / 1.5 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 40 °C
Multi-step reaction with 5 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3: toluene-4-sulfonic acid / dichloromethane / 20 °C 4: sodium ethanolate / ethanol / 1.5 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 40 °C
  • 29
  • [ 1339058-28-4 ]
  • [ 2283379-54-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C 4.1: sodium ethanolate / ethanol / 1.5 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 40 °C 6.1: hydrogenchloride / 0.5 h
Multi-step reaction with 6 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3: toluene-4-sulfonic acid / dichloromethane / 20 °C 4: sodium ethanolate / ethanol / 1.5 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 40 °C 6: hydrogenchloride / 0.5 h
  • 30
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4: sodium ethanolate / ethanol / 3 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere
Multi-step reaction with 6 steps 1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3: hydrogen; acetic acid / water / 20 °C 4: sodium ethanolate / ethanol / 3 h / 20 °C 5: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere
  • 31
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: dichloromethane / 0.42 h / 0 °C / Inert atmosphere 8.2: 0 - 20 °C / Inert atmosphere; Molecular sieve
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: dichloromethane / 0.42 h / 0 °C / Inert atmosphere 8.2: 0 - 20 °C / Inert atmosphere; Molecular sieve
  • 32
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C
Multi-step reaction with 6 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C
  • 33
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: dichloromethane / 1 h / 20 °C 4.2: 4 h / 20 °C
Multi-step reaction with 4 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: dichloromethane / 1 h / 20 °C 4.2: 4 h / 20 °C
  • 34
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C / Molecular sieve 8.2: 20 °C
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C / Molecular sieve 8.2: 20 °C
  • 35
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C / Molecular sieve 8.2: 20 °C 9.1: trifluoroacetic acid / dichloromethane / 0.5 h
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C / Molecular sieve 8.2: 20 °C 9.1: trifluoroacetic acid / dichloromethane / 0.5 h
  • 36
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: acetic acid / dichloromethane / 0.5 h / 20 °C 7.2: 2 h / 20 °C 8.1: trifluoroacetic acid; water / dichloromethane / 4 h / 20 °C 8.2: 1 h / 20 °C 8.3: 1 h
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: acetic acid / dichloromethane / 0.5 h / 20 °C 7.2: 2 h / 20 °C 8.1: trifluoroacetic acid; water / dichloromethane / 4 h / 20 °C 8.2: 1 h / 20 °C 8.3: 1 h
  • 37
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C 8.2: 1 h / 20 °C
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: trifluoroacetic acid; water / dichloromethane / 20 °C 8.1: acetic acid / dichloromethane / 1 h / 20 °C 8.2: 1 h / 20 °C
  • 38
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 10 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.1: magnesium sulfate / dichloromethane / 1 h / 20 °C 10.2: 1 h
Multi-step reaction with 10 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 10.1: magnesium sulfate / dichloromethane / 1 h / 20 °C 10.2: 1 h
  • 39
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
Multi-step reaction with 9 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: 1,2-dichloro-ethane / 1 h / 20 °C 6.2: 3 h / 20 °C 7.1: dmap / tetrahydrofuran / 2 h / 20 °C 8.1: potassium carbonate; bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II) / water; tetrahydrofuran / 20 °C / Inert atmosphere 9.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C
  • 40
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol; N,N-dimethyl-formamide / 38 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); caesium carbonate / water; tetrahydrofuran / 20 - 65 °C / Inert atmosphere 7.1: acetic acid / dichloromethane / 0.5 h 7.2: 1 h
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol; N,N-dimethyl-formamide / 38 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); caesium carbonate / water; tetrahydrofuran / 20 - 65 °C / Inert atmosphere 7.1: acetic acid / dichloromethane / 0.5 h 7.2: 1 h
  • 41
  • [ 1339058-28-4 ]
  • [ 2407638-80-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h
Multi-step reaction with 5 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h
  • 42
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.17 h 7.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 120 h / 65 °C 5.2: 0.17 h 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.17 h 7.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran
  • 43
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 48 h / 20 °C / Cooling with ice 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0 - 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere 8.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran
Multi-step reaction with 8 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: potassium acetate; bis(pinacol)diborane; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / 1,4-dioxane / 24 h / 65 °C / Inert atmosphere 2.2: 3407 / 3 h / pH 7 3.1: 1H-imidazole / N,N-dimethyl-formamide / 24 h / 45 °C 4.1: lithium hydroxide monohydrate / tetrahydrofuran 4.2: 0.17 h 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 65 °C 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 / water; tetrahydrofuran / Inert atmosphere 8.1: diethylazodicarboxylate; triphenylphosphine / tetrahydrofuran
  • 44
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: dichloromethane / 0.5 h / 20 °C 7.2: Molecular sieve
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: dichloromethane / 0.5 h / 20 °C 7.2: Molecular sieve
  • 45
  • [ 1339058-28-4 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: cesium fluoride; palladium diacetate; dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / 1,4-dioxane / 17.4 - 33 °C / Sealed tube; Inert atmosphere 3.1: [bis(acetoxy)iodo]benzene; 2,6-dimethylpyridine; osmium(VIII) oxide / water; tetrahydrofuran / 19.7 - 33 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: dichloromethane / 0.33 h / 20 °C 7.2: 0.67 h / 20 °C
Multi-step reaction with 7 steps 1.1: triphenylphosphine; diamide / tetrahydrofuran / 2.3 - 20 °C / Inert atmosphere 2.1: tetrakis(triphenylphosphine) palladium(0) / N,N-dimethyl-formamide / 70 °C / Inert atmosphere 3.1: hydrogen; acetic acid / water / 20 °C 4.1: sodium ethanolate / ethanol / 3 h / 20 °C 5.1: caesium carbonate / <i>tert</i>-butyl alcohol / 4 h / 65 °C 6.1: bis(di-tert-​butyl(4-​dimethylaminophenyl)​phosphine)​dichloropalladium(II); potassium phosphate / water; tetrahydrofuran / 20 °C / Sealed tube; Inert atmosphere 7.1: dichloromethane / 0.33 h / 20 °C 7.2: 0.67 h / 20 °C
  • 46
  • [ 1339058-28-4 ]
  • [ 2280987-10-0 ]
  • [ 2283377-50-2 ]
YieldReaction ConditionsOperation in experiment
With diamide; triphenylphosphine In tetrahydrofuran at 2.3 - 20℃; Inert atmosphere; 1.1L (R)-ethyl 2-acetoxy-3-(5-bromo-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate (R)-ethyl 2-acetoxy-3-(5-bromo-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate A 2 L three neck round bottom flask equipped with a temperature probe (J-KEM controlled) and stir bar was charged with Example 1K (40 g) and Example 1G (31.3 g) under nitrogen. The material was dissolved in anhydrous tetrahydrofuran (604 mL) at room temperature, and the reaction mixture was cooled to 2.3° C. in an ice bath. To the mixture was added triphenylphosphine (63.4 g). After about 15 minutes, (E)-N1,N1,N2,N2-tetramethyldiazene-1,2-dicarboxamide (41.6 g) was added in one portion. The temperature of the reaction did not rise significantly (temperature maintained at 2.5° C.). The reaction mixture was stirred at room temperature overnight. Thin-layer chromatography in 50% ethyl acetate/heptane indicated the starting materials were consumed, and a single major product had formed. The reaction mixture was filtered through a fritted Buchner funnel, and the material collected were washed with ethyl acetate. The filtrate was concentrated. The residue was dissolved in dichloromethane (150 mL), and loaded on to 2.2 L of silica gel that had been equilibrated in 30% ethyl acetate/heptane in a 3 L fritted Buchner funnel. The title compound was eluted with a gradient of 30-60% ethyl acetate in heptane. The early fractions were pure, but the later fractions were contaminated with triphenylphosphine oxide. The pure fractions were combined and were concentrated to provide the title compound. The impure fractions were combined and concentrated. The residue was dissolved in dichlormethane (50 mL) and purified on a Grace Reveleris X2 MPLC using a Teledyne Isco RediSep Rf gold 750 g silica gel column, eluting with 30-50% ethyl acetate/heptane. Pure fractions from this column were combined with the pure material from the earlier column. The material that resulted was mixed with diethyl ether (50 mL). The mixture was sonicated for 30 minutes and stirred for an additional 10 minutes. The material was filtered off, washed with diethyl ether, and dried to provide the title compound. Chiral SFC of this material on a HP/Aurora system using a ChiralCel OD-H column (4.6 mm*100 mm, 5 M) and a 5% to 50% methanol gradient over 10 minutes indicated a single peak with a retention time of 5.0 minutes. 1H NMR (400 MHz, dimethyl sulfoxide-d6) δ ppm 8.94 (d, 1H), 7.55 (m, 2H), 7.45 (m, 3H), 7.16 (m, 1H), 7.06 (m, 2H), 5.27 (d, 2H), 5.18 (dd, 1H), 4.07 (q, 2H), 3.77 (s, 3H), 3.29 (dd, 1H), 3.13 (dd, 1H), 2.02 (s, 3H), 1.10 (t, 3H). MS (ESI) m/z 529.1 (M+H)+.
  • 47
  • [ 1339058-28-4 ]
  • [ 2280992-06-3 ]
  • [ 2287188-01-4 ]
YieldReaction ConditionsOperation in experiment
With diamide; triphenylphosphine In tetrahydrofuran at 20℃; Cooling with ice; 18F Example 1 8F(R)-tert-butyl 2-acetoxy-3-(5-((tert-butyldimethylsilyl)oxy)-2-((2-(2-methoxyphenyl)pyrimidin-4-yl)methoxy)phenyl)propanoate To an oven dried 500 mL round bottom flask was added Example 18B (14.7 g),triphenylphosphine (27.4 g), Example 18E (20 g) and tetrahydrofuran (105 mL). The reaction flask was cooled in an ice bath. Solid (E)- N,N,N’,N’-tetramethyldiazene-1,2-dicarboxamide (18 g) was added and the reaction mixture was allowed to warm up to ambient temperature and was stirred overnight. The mixture was filtered and the filter cake was washed with tetrahydrofuran. The filtrate was concentrated. The residue was taken up in 200 mL of 15% ethyl acetate in heptanes, shaken, and filtered through 200 gsilica gel. The filtrate was concentrated and purified by silica gel chromatography on a Grace Reveleris X2 MPLC system using a Teledyne Isco RediSep Rf gold 330 g silica column with 20-50% ethyl acetate/heptanes. Fractions containing desired product were combined and concentrated to obtain the title compound. ‘H NMR (501 MHz, chloroform-d) ppm 8.89 (d, 1H), 7.70 (dd, 1H), 7.63 (d, lH), 7.47-7.41 (m, lH), 7.09 (It, IH), 7.05 (d, IH), 6.79-6.73 (m, 2H), 6.70 (dd, 1H), 5.25 (dd, lH), 5.20 (d,2H), 3.88 (s, 3H), 3.40 (dd, 1 H), 3.00 (dd, 11-1), 2.06 (s, 3H), 1.47 (s, 9H), 0.99 (s, 9H), 0.18 (s, 6H). MS (ES) m/z 609.2 [M+HJ.
  • 48
  • [ 1339058-28-4 ]
  • [ 4344-87-0 ]
  • [ 2459518-17-1 ]
YieldReaction ConditionsOperation in experiment
69% With di-tert-butyl-diazodicarboxylate; triphenylphosphine In tetrahydrofuran at 45℃; for 16h; 1.1 first step; 2-(2-methoxyphenyl)-4-(((5-methyl-1H-pyrazol-3-yl)oxy)methyl)pyrimidine 1c Combine 5-methyl-1H-pyrazole-3-ol 1a (1.00 g, 10.19 mmol, Shaoyuan) and triphenylphosphine (3.60 g, 13.7 mmol)And (2-(2-methoxyphenyl)pyrimidin-4-yl)methanol 1b (2.00 g, 9.25 mmol,It is prepared by the method disclosed in the patent application "WO201715224") dissolved in 30mL of tetrahydrofuran,Then, di-tert-butyl azodicarboxylate (3.20 g, 13.9 mmol) was added to the reaction liquid, and the reaction liquid was heated to 45° C. and stirred for 16 hours.The reaction solution was cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with eluent system B.The title product 1c (1.90 g) was obtained, yield: 69%.
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