Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([NH:16][CH2:17][CH:18]([OH:28])[C:19]2[N:20]=[C:21]([C:24]([F:27])([F:26])[F:25])[S:22][CH:23]=2)[CH3:15])=[CH:9][CH:8]=1)([O:3][CH3:4])=[O:2].Cl[CH2:30][C:31](Cl)=[O:32].[H-].[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:1]([CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([N:16]2[C:31](=[O:32])[CH2:30][O:28][CH:18]([C:19]3[N:20]=[C:21]([C:24]([F:26])([F:27])[F:25])[S:22][CH:23]=3)[CH2:17]2)[CH3:15])=[CH:9][CH:8]=1)([O:3][CH3:4])=[O:2]
Reactant: COC(=O)COc1ccc(CC(C)NCC(O)c2csc(C(F)(F)F)n2)cc1
Reactant: O=C(Cl)CCl
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)COc1ccc(CC(C)N2CC(c3csc(C(F)(F)F)n3)OCC2=O)cc1

Procedure:
Prepared by analogy to Example 74a by reaction of N-[2-(4-Carbomethoxymethoxyphenyl)-1-methylethyl]-2-hydroxy-2-(2-trifluoromethyl-thiazol-4-yl)ethanamine (diastereomer B), chloroacetyl chloride and sodium hydride, and purification of the base on a silica gel column using toluene/ethyl acetate =6:4 as eluant.
Reaction SMILES: C(C1N=C(N2CCOCC2)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.[C:28]([C:32]1[N:33]=[C:34](Cl)[C:35]2[N:40]=[N:39][N:38]([CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[Cl:48])[C:36]=2[N:37]=1)([CH3:31])([CH3:30])[CH3:29].[CH3:50][C:51]1([CH3:57])[O:56][CH2:55][CH2:54][NH:53][CH2:52]1>>[C:28]([C:32]1[N:33]=[C:34]([N:53]2[CH2:54][CH2:55][O:56][C:51]([CH3:57])([CH3:50])[CH2:52]2)[C:35]2[N:40]=[N:39][N:38]([CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=3[Cl:48])[C:36]=2[N:37]=1)([CH3:31])([CH3:30])[CH3:29]
Reactant: CC1(C)CNCCO1
Reactant: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Agent: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Product: CC1(C)CN(c2nc(C(C)(C)C)nc3c2nnn3Cc2ccccc2Cl)CCO1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 2,2-dimethylmorpholine and isolated as colorless gum (13.7 mg, 70%). MS (m/e): 415.4 (MH+).
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]45[CH2:31][CH2:30][C:27]([CH2:32][C:33]([O-:35])=[O:34])([CH2:28][CH2:29]4)[O:26][CH2:25]5)=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)=[O:10])=[C:6]([CH3:8])[N:7]=1)[CH3:2].[Li+].[OH-].Cl>C1COCC1.O>[CH2:1]([C:3]1[O:4][C:5]([C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]45[CH2:29][CH2:28][C:27]([CH2:32][C:33]([OH:35])=[O:34])([CH2:30][CH2:31]4)[O:26][CH2:25]5)=[CH:20][CH:19]=3)=[CH:16][CH:17]=2)=[O:10])=[C:6]([CH3:8])[N:7]=1)[CH3:2]
Reactant: CCc1nc(C)c(C(=O)Nc2ccc(-c3ccc(C45CCC(CC(=O)[O-])(CC4)OC5)cc3)cc2)o1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCc1nc(C)c(C(=O)Nc2ccc(-c3ccc(C45CCC(CC(=O)O)(CC4)OC5)cc3)cc2)o1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87 %

Procedure:
To a solution of 2-(4-(4′-(2-ethyl-4-methyloxazole-5-carboxamido)-[1,1′-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (159 mg, 0.325 mmol) in THF (3 ml) at room temperature was added 1N LiOH (0.391 ml, 0.391 mmol). The mixture was stirred at room temperature overnight. The mixture was quenched with 1N HCl (0.391 ml, 0.391 mmol) and diluted with H2O. The THF was removed in vacuo to afford off-white slurry. The slurry was stirred for 15 min then filtered. The filter cake was washed with H2O, heptane, and dried to afford the title compound as off-white sold (135 mg, 87% yield).
Reaction SMILES: [F:1][C:2]1[C:15]([N:16]=[C:17]=[O:18])=[CH:14][C:5]2[N:6]([CH2:11][C:12]#[CH:13])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.[OH:19][CH:20]([C:25]([CH3:27])=[CH2:26])[C:21]([O:23]C)=O.C1CCN2C(=NCCC2)CC1.O>C1C=CC=CC=1>[F:1][C:2]1[C:15]([N:16]2[C:21](=[O:23])[C:20](=[C:25]([CH3:27])[CH3:26])[O:19][C:17]2=[O:18])=[CH:14][C:5]2[N:6]([CH2:11][C:12]#[CH:13])[C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1
Reactant: C#CCN1C(=O)COc2cc(F)c(N=C=O)cc21
Reactant: C=C(C)C(O)C(=O)OC
Solvent: O
Solvent: c1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: C#CCN1C(=O)COc2cc(F)c(N3C(=O)OC(=C(C)C)C3=O)cc21
Temperature: 25 °C

Procedure:
To a solution of 7-fluoro-6-isocyanato-4-propargyl-2H-1,4-benzoxazin-3(4H)-one (2.5 g) and methyl 2-hydroxy-3-methyl-3-butenoate (1.3 g) in benzene (50 ml), DBU (1.5 g) was added at room temperature. The resulting mixture was refluxed for 10 hours, cooled to room temperature, combined with water and extracted with ethyl acetate. The organic layer was washed with water, dried over magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography using a mixture of toluene and ethyl acetate as the eluent to give Compound No. 9 (3.0 g).
Reaction SMILES: Br[CH:2](Br)[CH3:3].[CH3:5][O:6][C:7]1[CH:13]=[CH:12][CH:11]=[C:9]([OH:10])[C:8]=1[OH:14]>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.O.[OH-].[Na+]>[CH3:5][O:6][C:7]1[C:8]2[O:14][CH2:3][CH2:2][O:10][C:9]=2[CH:11]=[CH:12][CH:13]=1
Reactant: COc1cccc(O)c1O
Reactant: CC(Br)Br
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: [Br-]
Agent: [Na+]
Solvent: O
Product: COc1cccc2c1OCCO2

Procedure:
A mixture of dibromoethane (10.73 g, 77 mmol) and cetyltrimethylammonium bromide (0.291 g, 0.8 mmol) in 5 cm3 of water is brought to reflux. A solution of 3-methoxycatechol (5 g, 35.7 mmol) in 20N sodium hydroxide (NaOH, 4 g in 5 cm3 of water) is added slowly. The mixture is stirred at the reflux for 12 hours and then, after cooling and extraction with ether, purification on a silica column (eluent: petroleum ether/ether, 9:1) enables 7.4 g of a colorless oil to be isolated
Reaction SMILES: [OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][N:24](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([SiH](CC)CC)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:1][C:2]([CH3:47])([CH3:46])[C@@H:3]([NH:10][C:11]([NH:13][C:14]1[N:19]=[C:18]([CH2:20][OH:21])[C:17]2[C:22]([O:44][CH3:45])=[N:23][NH:24][C:16]=2[CH:15]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(NC(=O)N[C@@H](c3ccccc3)C(C)(C)O)nc(CO)c12
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1n[nH]c2cc(NC(=O)N[C@@H](c3ccccc3)C(C)(C)O)nc(CO)c12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (533 mg, 0.849 mmol) was dissolved in DCM (3 ml), charged with triethylsilane (0.271 ml, 1.698 mmol) followed by TFA (3.27 ml, 42.5 mmol) and allowed to stir for 1 h at rt. The solvents were removed in vacuo and the residue was dissolved in 25 mL 10:1 EtOAc/MeOH and washed with 20 mL saturated sodium bicarbonate. The aq. was extracted 1×15 mL EtOAc and the combine organics were washed with brine, dried over sodium sulfate, concentrated vacuo and purified on silica gel 5-15% MeOH/DCM to provide (S)-1-(2-hydroxy-2-methyl-1-phenylpropyl)-3-(4-(hydroxymethyl)-3-methoxy-1H-pyrazolo[4,3-c]pyridin-6-yl)urea (110) as a white solid. MS: [M+H]+ m/z 386. 1H NMR (600 MHz, dmso) δ 12.00 (s, 1H), 9.20 (s, 1H), 7.31 (m, 2H), 7.25 (m, 2H), 7.15 (m, 1H), 7.07 (br s, 1H), 5.00 (t, J=6.0, 1H), 4.74 (d, J=6.0, 2H), 4.68 (s, 1H), 4.59 (d, J=9.0, 1H), 3.93 (s, 3H), 1.13 (s, 3H), 1.12 (s, 3H).
Reaction SMILES: [OH-].[K+].[F:3][C:4]1[CH:5]=[CH:6][C:7]([O:14][CH3:15])=[C:8]2[C:12]=1[NH:11][N:10]=[C:9]2[NH2:13].Cl[CH2:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=1)[C:21]#[N:22].O>CS(C)=O.ClCCl>[NH2:13][C:9]1[C:8]2[C:12](=[C:4]([F:3])[CH:5]=[CH:6][C:7]=2[O:14][CH3:15])[N:11]([CH2:17][C:18]2[CH:19]=[C:20]([CH:23]=[CH:24][CH:25]=2)[C:21]#[N:22])[N:10]=1
Reactant: COc1ccc(F)c2[nH]nc(N)c12
Reactant: N#Cc1cccc(CCl)c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Solvent: CS(C)=O
Product: COc1ccc(F)c2c1c(N)nn2Cc1cccc(C#N)c1
Reaction time: 0.5 h
Yield: 56 %

Procedure:
To a fine suspension of ground potassium hydroxide (566 mg, 10.09 mmol) in dimethyl sulfoxide (5 mL) at room temperature under nitrogen was added a solution of 7-fluoro-4-(methyloxy)-1H-indazol-3-amine (for a preparation see Intermediate 43) (727 mg, 4.01 mmol) in dimethyl sulfoxide (2 mL). After 5 min the resulting dark brown solution was treated with 3-(chloromethyl)benzonitrile (730 mg, 4.82 mmol). The reaction mixture was stirred for 30 min and then the mixture was poured into water, forming an emulsion. This was extracted with DCM and the combined extracts were washed with water and passed through a hydrophobic frit. The aqueous was extracted with ethyl acetate and the combined organic solutions were washed with water and brine, dried (Na2SO4) and then combined with the initial DCM extracts and concentrated in vacuo to leave a brown oil. The residue was loaded in dichloromethane to a silica 100 g cartridge and purified by chromatography on Flashmaster eluting with 0-100% ethyl acetate-cyclohexane over 40 min. The appropriate fractions were combined and evaporated in vacuo to give the required product (665 mg, 56%) as a yellow powder. LCMS (System A) RT=1.02 min, ES+ve m/z 297 (M+H)+.
Reaction SMILES: C(O[CH:5]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8](=[O:22])[C@@H:7]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6]1)(=O)C>C(O)C.[Pd]>[C:27]([O:26][C:24]([NH:23][C@H:7]1[CH2:6][CH2:5][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8]1=[O:22])=[O:25])([CH3:30])([CH3:29])[CH3:28]
Reactant: CCOC(=O)CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)CC(OC(C)=O)c2ccccc21
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)CCc2ccccc21

Procedure:
A solution of 5-acetoxy-3-(S)-t-butyloxycarbonylamino-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (0.7 g) in ethanol (50 ml) was hydrogenated at 42 psi for 24 hours at 70° using 10% palladium on charcoal (0.5 g) as catalyst. The catalyst was filtered off and the solvent removed under reduced pressure to give 3-(S)-t-butyloxycarbonylamino-1-ethoxycarbonylmethyl-2,3,4,5 tetrahydro-1H-[1]benzazepin-2-one which, without further purification was converted to 3-(S)-amino-1-ethoxycarbonylmethyl-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one by the procedure described above; m.p. 99°-101°, [α]D =-297° (c=1 in ethanol).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:32])=[C:6]([NH:8][C:9]2[CH:14]=[C:13]([NH:15][CH:16]3[CH2:18][CH2:17]3)[N:12]3[N:19]=[CH:20][C:21](/[CH:22]=[C:23]4/[C:24](=[O:31])[N:25]([CH2:29][OH:30])[C:26](=[O:28])[NH:27]/4)=[C:11]3[N:10]=2)[CH:7]=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42](O)=[O:43])[CH2:36][CH2:35]1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C=O)C.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40][CH2:41][C:42]([O:30][CH2:29][N:25]2[C:24](=[O:31])/[C:23](=[CH:22]/[C:21]3[CH:20]=[N:19][N:12]4[C:13]([NH:15][CH:16]5[CH2:17][CH2:18]5)=[CH:14][C:9]([NH:8][C:6]5[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=5[F:32])=[N:10][C:11]=34)/[NH:27][C:26]2=[O:28])=[O:43])[CH2:36][CH2:35]1
Reactant: CN1CCN(CCC(=O)O)CC1
Reactant: O=C1N/C(=C\c2cnn3c(NC4CC4)cc(Nc4cc(Cl)ccc4F)nc23)C(=O)N1CO
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1CCN(CCC(=O)OCN2C(=O)N/C(=C\c3cnn4c(NC5CC5)cc(Nc5cc(Cl)ccc5F)nc34)C2=O)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 26.2 %

Procedure:
To (Z)-5-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-3-(hydroxymethyl)imidazolidine-2,4-dione (100 mg, 0.218 mmol) in DMF (3 mL) was added 3-(4-methylpiperazin-1-yl)propanoic acid (75 mg, 0.436 mmol), dicyclohexylcarbodiimide (90 mg, 0.436 mmol), and DMAP (4.0 mg, 0.33 mmol). The reaction mixture was stirred at room temperature overnight and then diluted with ethyl acetate and washed 1× water, 3× brine. The organic layer was dried with MgSO4, filtered and adsorbed onto silica gel. The crude material was purified by column chromatography eluting with 0-10% MeOH/CH2Cl2 gradient. Pure fractions were combined and the solvent was removed. This material was crystallized from ethyl acetate and hexane to provide 35 mg (26%) of (Z)-(4-((5-(5-chloro-2-fluorophenylamino)-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-3-yl)methylene)-2,5-dioxoimidazolidin-1-yl)methyl 3-(4-methylpiperazin-1-yl)propanoate as a yellow solid. LCMS (ES): >95% pure, m/z 612 [M+1]+.
Reaction SMILES: Cl[C:2](Cl)([O:4][C:5](=[O:11])[O:6][C:7](Cl)(Cl)Cl)Cl.C(N([CH2:18][CH3:19])CC)C>>[C:5]([C:18]1([CH3:19])[CH2:7][O:6][C:5](=[O:11])[O:4][CH2:2]1)([O:4][CH3:2])=[O:6]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CCN(CC)CC
Product: COC(=O)C1(C)COC(=O)OC1

Procedure:
As set out hereinabove, the binder component of the dispersion of the invention is an organic polycarbonate polymer. The resulting polymer of the polymerization of 5-carbomethoxy-5-methyl-1,3-dioxan-2-one may be used as a component of the polymer binder. The polycarbonate polymer of 5-carbomethoxy-5-methyl-1,3-dioxan-2-one may be prepared as disclosed in Weilandt, K. D., Keul, H. and Hocker, H., Macromol. Chem. Phys. 197, 3851-3868 (1996). 5-Carbomethoxy-5-methyl-1,3-dioxan-2-one may be prepared via the reaction of 2,2-bis(hydroxymethyl)propionic acid with methanol to give methyl 2,2-bis(hydroxymethyl)propionate, which was then reacted with triphosgene in the presence of triethylamine to afford the desired product, 5-carbomethoxy-5-methyl-1,3-dioxan-2-one, as a white solid.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:29]=[CH:30][C:31]=1[NH:32][S:33]([CH2:36][CH2:37][CH3:38])(=[O:35])=[O:34])[C:8]([C:10]1[N:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]2=[C:12]([C:19]2[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=2)[C:22]([O:24]C)=[O:23])[N:11]=1)=[O:9]>CO>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:29]=[CH:30][C:31]=1[NH:32][S:33]([CH2:36][CH2:37][CH3:38])(=[O:35])=[O:34])[C:8]([C:10]1[N:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]2=[C:12]([C:19]2[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=2)[C:22]([OH:24])=[O:23])[N:11]=1)=[O:9]
Reactant: CCCS(=O)(=O)Nc1ccc(C(=O)c2nc(-c3cccc(C(=O)OC)c3)c3ccccn23)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCS(=O)(=O)Nc1ccc(C(=O)c2nc(-c3cccc(C(=O)O)c3)c3ccccn23)cc1OC
Temperature: 70 °C

Procedure:
1.4 ml of a 1N aqueous sodium hydroxide solution are added to 0.34 g (0.7 mmol) of methyl 3-(3-{3-methoxy-4-[(propylsulfonyl)amino]benzoyl}imidazo[1,5-a]pyridin-1-yl)benzoate obtained in example 190 in 20 ml of methanol. The reaction medium is heated at 70° C. for 3 hours and then concentrated under reduced pressure. The residue is taken up in water and the aqueous phase obtained is washed with dichloromethane, neutralized by addition of 1.4 ml of 1N hydrochloric acid and then extracted with dichloromethane. The organic phase obtained is dried over sodium sulfate and concentrated under reduced pressure. 0.19 g of a yellow solid is collected, which solid is salified in the sodium salt.2.1H2O form. Melting point: 145° C.; 1H NMR (d6-DMSO): 0.96-1.01 (3H, t), 1.71-1.83 (2H, m), 3.16-3.19 (2H, m), 4.00 (3H, s), 7.33-7.70 (2H, m), 7.36-7.38 (1H, m), 7.52-7.97 (2H, m), 8.04-8.07 (2H, m), 8.27-9.85 (2H, m), 8.44 (1H, s), 8.64 (1H, s), 9.25 (1H, m)
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([CH:17]([CH3:19])[CH3:18])[C:9]=2[CH:20]=O)=[CH:4][CH:3]=1.[C:22]([CH:26]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([O:24][CH3:25])=[O:23]>CO>[CH3:25][O:24][C:22](=[O:23])/[CH:26]=[CH:20]/[C:9]1[N:10]([CH:17]([CH3:18])[CH3:19])[C:11]2[C:16]([C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)=[CH:15][CH:14]=[CH:13][CH:12]=2
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)n1c(C=O)c(-c2ccc(F)cc2)c2ccccc21
Solvent: CO
Product: COC(=O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.2 %

Procedure:
As in Example 226, the impure 3-(4-fluorophenyl)- 1-(1-methylethyl)-1H-indole-2-carboxaldehyde (5.56 g) from the previous example was reacted in methanol (75 mL) with (carbomethoxymethylene)triphenylphosphorane (6.2 g) was stirred at room temperature for 1 hour. The pale yellow solids that formed were filtered and washed with cold methanol to furnish 4.58 g of (E)-3-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-2-propenoic acid methyl ester. A sample was crystallized from dichloromethane-hexane to yield the analytical specimen, mp 155°-157° C.
Reaction SMILES: [C:1]1([C:7]2[O:8][C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:17]([N:19]([CH2:32][CH3:33])[CH2:20][CH2:21][O:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26])[CH3:18]>>[CH2:32]([N:19]([CH2:17][CH3:18])[CH2:20][CH2:21][O:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25]([C:11]1[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[O:8][C:7]=1[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:26])[CH3:33]
Reactant: c1ccc(-c2cc3ccccc3o2)cc1
Reactant: CCN(CC)CCOc1ccccc1C(=O)Cl
Agent: Cl
Product: CCN(CC)CCOc1ccccc1C(=O)c1c(-c2ccccc2)oc2ccccc12

Procedure:
Acylation of 2-phenylbenzofuran with 2-(2-diethylaminoethoxy)benzoyl chloride hydrochloride by the procedure described in Example 6 gives the title compound.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][C:7](B(O)O)=[CH:8][CH:9]=2)[CH:4]=[N:3]1.[Br:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](Br)[N:16]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CCOC(C)=O>[Br:14][C:15]1[N:16]=[C:17]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[N:2]([CH3:1])[N:3]=[CH:4]3)[CH:18]=[CH:19][CH:20]=1
Reactant: Cn1ncc2cc(B(O)O)ccc21
Reactant: Brc1cccc(Br)n1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cn1ncc2cc(-c3cccc(Br)n3)ccc21
Temperature: 110 °C

Procedure:
In a 10-20 mL reaction vial, the 1-methyl-1H-indazol-5-ylboronic acid (500 mg, 2.73 mmol) and the 2,6-dibromopyridine (776 mg, 3.27 mmol) were dissolved in dioxane (7 mL) under argon atmosphere. The mixture was bubbled with argon for 5 min and then potassium carbonate (754 mg, 5.46 mmol) and PdCl2(dppf) catalyst were added sequentially. The resulting reaction mixture was then sealed and heated in oil bath at 110° C. for 3 h. Reaction was then diluted with EtOAc (10 mL), filtered and the filtrate was collected and concentrated. Residue was purified on silica gel column with 0-25% EtOAc/Hex to afford the title product. LCMS-ESI+: calc'd for: C13H10BrN3: 288.0, 290.0 (M+H+); Found: 288.2, 290.3 (M+H+).
Reaction SMILES: [Na].C[O-].[Na+].Cl.[NH2:6][C:7]([NH2:9])=[NH:8].CN(C)[CH:12]=[CH:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[OH:22])=O>CO>[NH2:8][C:7]1[N:9]=[C:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[OH:22])[CH:13]=[CH:12][N:6]=1
Reactant: N=C(N)N
Reactant: CN(C)C=CC(=O)c1ccccc1O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: Nc1nccc(-c2ccccc2O)n1
Yield: 86.8 %

Procedure:
Sodium (1.21 g, 52.6 mmol) is added to 200 ml methanol to prepare a solution of sodium methoxide. After addition of guanidine hydrochloride (12.41 g, 129.9 mmol) and 3-(dimethylamino)-1-(2-hydroxyphenyl)-2-propen-1-one (5.0 g, 26.15 mmol; J. Heterocyclic Chem., 14:345, 1977) the mixture is heated at reflux over night. The reaction solvent is removed under reduced pressure, and the residue treated with water. The resulting precipitate is collected by filtration and dried in vacuo to give 4.25 g of 2-amino-4-(2-hydroxyphenyl)pyrimidine (87%). This pyrimidine pre-cursor is reacted with (2S)-glycidyl 3-nitrobenzenesulfonate substantially as described for Epoxide 1 to give 2.05 g of the title epoxide (37.5%).
Reaction SMILES: [OH:1][C:2]([CH3:33])([CH3:32])/[CH:3]=[CH:4]/[CH:5]=[CH:6]/[C:7]([C:10]1[CH:11]=[C:12]([CH:29]=[CH:30][CH:31]=1)[O:13][CH2:14][C:15]1[CH:16]=[C:17]([C:25](OC)=[O:26])[C:18](=[CH:23][CH:24]=1)[C:19](OC)=[O:20])([CH3:9])[CH3:8].[BH4-].[Li+]>>[OH:26][CH2:25][C:17]1[CH:16]=[C:15]([CH:24]=[CH:23][C:18]=1[CH2:19][OH:20])[CH2:14][O:13][C:12]1[CH:11]=[C:10]([C:7]([CH3:8])([CH3:9])/[CH:6]=[CH:5]/[CH:4]=[CH:3]/[C:2]([CH3:33])([OH:1])[CH3:32])[CH:31]=[CH:30][CH:29]=1
Reactant: COC(=O)c1ccc(COc2cccc(C(C)(C)/C=C/C=C/C(C)(C)O)c2)cc1C(=O)OC
Agent: [BH4-]
Agent: [Li+]
Product: CC(C)(O)/C=C/C=C/C(C)(C)c1cccc(OCc2ccc(CO)c(CO)c2)c1

Procedure:
In a manner similar to Example 53(e), by reacting 360 mg (0.8 mmol) of dimethyl 4-[3-((2E,4E)-6-hydroxy-1,1,6-trimethylhepta-2,4-dienyl)phenoxymethyl]phthalate (prepared from the previous product in a manner similar to Example 64(d)) with 70 mg (3.2 mmol) of lithium borohydride, a colourless oil is obtained (m=220 mg; Y=70%).
Reaction SMILES: [C:1]([C:4]1[CH:33]=[CH:32][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]([O:25][CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)[C:17]3[CH:18]=[C:19]([CH:22]=[CH:23][CH:24]=3)[C:20]#[N:21])=[CH:12][CH:11]=2)=[C:6]([CH2:34][CH3:35])[C:5]=1[OH:36])(=[O:3])[CH3:2].[N-:37]=[N+:38]=[N-:39].[Na+].Cl.C(N(CC)CC)C>>[CH2:34]([C:6]1[C:5]([OH:36])=[C:4]([C:1](=[O:3])[CH3:2])[CH:33]=[CH:32][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([O:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[C:17]2[CH:24]=[CH:23][CH:22]=[C:19]([C:20]3[N:37]=[N:38][NH:39][N:21]=3)[CH:18]=2)=[CH:12][CH:11]=1)[CH3:35]
Reactant: CCc1c(OCc2ccc(C(OC3CCCCO3)c3cccc(C#N)c3)cc2)ccc(C(C)=O)c1O
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Product: CCc1c(OCc2ccc(C(OC3CCCCO3)c3cccc(-c4nn[nH]n4)c3)cc2)ccc(C(C)=O)c1O

Procedure:
Employing the procedure of Example 1 using 3-[[4-(4-acetyl-2-ethyl-3-hydroxy-phenoxymethyl)-phenyl]-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (869 mg, 1.79 mmol), sodium azide (1.16 g, 17.9 mmol), and triethylamine hydrochloride (2.46 g, 17.9 mmol), the title product is obtained as a clear oil (900 mg, 66%): MS (esi negative) m/z (rel intensity) 527 (100).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[C:12](Cl)(=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].C(N(CC)CC)C.O>CN(C=O)C>[C:12]([C:9]1[CH:10]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:6]=[CH:7][C:8]=1[OH:11])(=[O:24])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: CC(=O)Nc1ccc(O)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCC(=O)c1cc(NC(C)=O)ccc1O
Temperature: 25 °C
Yield: 12 %

Procedure:
An equivalent amount in moles of para-acetylaminophenol and lauroyl chloride are placed in contact at 0° C. in DMF (dilution=15%) in the presence of one molar equivalent of triethylamine. The mixture is allowed to warm to room temperature with stirring and the reaction medium is then poured into water and the product precipitates. It is washed with heptane and then dried under vacuum. The yield is 12%. The elemental analysis is in accordance with the structure.