Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N:9]1[C:17]2[CH:16]=[CH:15][C:14]([C:18]#[N:19])=[C:13]3[CH2:20][CH:21]([N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])[CH2:22][CH:11]([C:12]=23)[CH2:10]1)(=O)C1C=CC=CC=1.C([Li])CCC.Cl>C1COCC1.CCCCCC>[C:18]([C:14]1[CH:15]=[CH:16][C:17]2[NH:9][CH2:10][CH:11]3[CH2:22][CH:21]([N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])[CH2:20][C:13]=1[C:12]=23)#[N:19]
Reactant: CCCN(CCC)C1Cc2c(C#N)ccc3c2C(C1)CN3C(=O)c1ccccc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCCN(CCC)C1Cc2c(C#N)ccc3c2C(CN3)C1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 113.8 %

Procedure:
To a stirred solution of 4.8 g (0.0124 mol) of (±)-1-benzoyl-6-cyano-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz[cd]indole in 200 mL of THF cooled to -78° C. under a N2 atmosphere were added 16 mL (0.025 mol) of a 1.6M solution of n-butyl lithium in hexane. The reaction mixture was stirred at -78° C. for 30 minutes and then allowed to warm to -20° C. To the reaction mixture was added 100 mL of 1N HCl. The mixture was extracted once with ethyl ether. The acidic solution was made alkaline with the addition of cold 5N NaOH. The basic mixture was extracted twice with CH2 Cl2. The combined organic solution was washed with a saturated NaCl solution. The CH2Cl2 solution was dried over MgSO4 and evaporated to give 4 g of an oil. Chromatography of this oil over silica gel with ethyl acetate as eluent gave 3 g (85%) of product as an oil which upon standing solidified.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:24]=[CH:23][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=3)[C:18]#[N:19])[O:12][C:13]=2[CH3:14])=[C:5]([O:25][CH3:26])[CH:4]=1.[OH:27][C:28]1[C:32]([CH:33]=[O:34])=[CH:31][N:30]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[N:29]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH:33]([C:32]1[C:28]([O:27][CH2:2][C:3]2[CH:24]=[CH:23][C:6]([O:7][CH2:8][C:9]3[N:10]=[C:11]([C:15]4[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=4)[C:18]#[N:19])[O:12][C:13]=3[CH3:14])=[C:5]([O:25][CH3:26])[CH:4]=2)=[N:29][N:30]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=1)=[O:34]
Reactant: O=Cc1cn(-c2ccccc2)nc1O
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2cccc(C#N)c2)oc1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(COc2nn(-c3ccccc3)cc2C=O)ccc1OCc1nc(-c2cccc(C#N)c2)oc1C
Temperature: 80 °C
Reaction time: 2 h
Yield: 95.8 %

Procedure:
A mixture of 3-[4-{(4-chloromethyl-2-methoxyphenoxy)methyl}-5-methyl-1,3-oxazol-2-yl]benzonitrile (4.32 g), 3-hydroxy-1-phenyl-1H-pyrazole-4-carbaldehyde (2.0 g), anhydrous potassium carbonate (1.47 g) and N,N-dimethylformamide (100 mL) was stirred at 80° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated to give 3-{4-[(4-{[(4-formyl-1-phenyl-1H-pyrazol-3-yl)oxy]methyl)-2-methoxyphenoxy}methyl]-5-methyl-1,3-oxazol-2-yl}benzonitrile (5.30 g, yield 96%) as colorless crystals. Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 161-162° C.
Reaction SMILES: SC1C=CC(S[C:9]2[CH:14]=[CH:13][C:12]([C:15](=[O:25])[C:16]([CH3:24])([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH3:17])=[CH:11][CH:10]=2)=CC=1.[SH:26][CH2:27][CH:28]([OH:33])[CH:29]([OH:32])[CH2:30][SH:31].C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[OH:33][CH:28]([CH:29]([OH:32])[CH2:30][SH:31])[CH2:27][S:26][C:9]1[CH:10]=[CH:11][C:12]([C:15](=[O:25])[C:16]([CH3:17])([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)[CH3:24])=[CH:13][CH:14]=1
Reactant: OC(CS)C(O)CS
Reactant: CC(C)(C(=O)c1ccc(Sc2ccc(S)cc2)cc1)N1CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(C)(C(=O)c1ccc(SCC(O)C(O)CS)cc1)N1CCOCC1
Reaction time: 17 h

Procedure:
1.0 g (4.0 mmol) of 1-[4-(4-mercaptophenylthio)phenyl]-2-methyl-2-morpholine-4-yl-propane-1-one and 1.37 g (8.9 mmol) of 1,4-dimercapto-2,3-butanediol are dissolved in 50 ml of dry dimethylacetamide, 1.10 g (8.0 mmol) of potassium carbonate are added and the mixture is stirred for 17 h. The resulting suspension is poured into water and extracted with ethyl acetate, the combined organic phases are washed with water. The solvent is distilled off and the residual oil is purified by column chromatography on silica gel with ethanol-methylene chloride (5:95) as eluent. The structure is confirmed by the 1H-NMR-spectrum, measured in CDCl3. The signals (δ in ppm) are 1.31 (s,6H), 1.55 (t,1 H), 2.57 (m,4H), 2.75 (m, 1H), 3.24 (m,5H), 3.70 (m,5H), 4.18 (s,1H), 7.53 (d,2H), 8.49 (d,2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[NH:12]([CH2:16][CH2:17][OH:18])[CH2:13][CH2:14][OH:15]>CS(C)=O>[OH:15][CH2:14][CH2:13][N:12]([C:7]1[CH:6]=[CH:5][C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]=1[Cl:1])[CH2:16][CH2:17][OH:18]
Reactant: O=[N+]([O-])c1ccc(F)c(Cl)c1
Reactant: OCCNCCO
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccc(N(CCO)CCO)c(Cl)c1
Temperature: 140 °C
Yield: 63.9 %

Procedure:
Dissolved in 8 ml of DMSO were 10.0 g (57.0 mmol) of 3-chloro-4-fluronitrobenzene and 8.6 g (82 mmol) of diethanolamine. The thus-obtained mixture was stirred under heat for 2 hours at 140° C., followed by extraction with ethyl acetate. The solvent was distilled out under reduced pressure, whereby 9.5 g of the title compound were obtained as a yellow oil (yield: 64%).
Reaction SMILES: [CH3:1][C@@H:2]([NH2:5])[CH2:3][CH3:4].C(N(CC)CC)C.[Cl:13][CH2:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][CH:23]=1)[C:18](Cl)=[O:19]>ClCCl>[C@H:2]([NH:5][C:18](=[O:19])[C:17]1[CH:21]=[CH:22][CH:23]=[C:15]([CH2:14][Cl:13])[CH:16]=1)([CH2:3][CH3:4])[CH3:1]
Reactant: O=C(Cl)c1cccc(CCl)c1
Reactant: CC[C@@H](C)N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC[C@@H](C)NC(=O)c1cccc(CCl)c1
Reaction time: 2 h
Yield: 77.8 %

Procedure:
A solution of (R)-butan-2-amine (14.77 mmol, 1.478 mL, 1,081 g) and triethylamine (15.48 mmol, 2.157 mL, 1.566 g) in dichloromethane was added dropwise to a stirred solution of 3-(chloromethyl)benzoyl chloride (14.07 mmol, 2 mL, 2.66 g) in dichloromethane at room temperature. Upon complete addition the reaction was stirred for 2 hours, after which time the solvent was removed under vacuum and ethyl acetate (100 mL) added. The organic solution was then washed with water (200 mL), dried over sodium sulphate and concentrated under vacuum to give the title compound (2.47 g) as a cream solid. MS (ESI) m/z 226.3[M+H]+
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]=[CH2:10].[Br:11][C:12]1[CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[C:15]([F:18])=[N:16][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Br:11][C:12]1[CH:13]=[C:14](/[CH:10]=[CH:9]/[C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[C:15]([F:18])=[N:16][CH:17]=1
Reactant: CC1(C)OB(c2cc(Br)cnc2F)OC1(C)C
Reactant: C=Cc1cc(F)ccc1F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: Fc1ccc(F)c(/C=C/c2cc(Br)cnc2F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A round bottom flask was charged with 1,4-difluoro-2-vinylbenzene (1 g, 7.14 mmol), 5-bromo-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.69 g, 8.92 mmol), and DMF (27 mL). The resulting mixture was purged with a stream of oxygen for 10 min. To this was added sodium carbonate (1.89 g, 17.8 mmol) and palladium (II) acetate (0.128 g, 0.571 mmol) as a solid in a single portion. The reaction was purged with oxygen for 5 min. The reaction was fitted with a balloon of oxygen and stirred at room temperature overnight. In the morning, the reaction was diluted with ethyl acetate and poured into water. The mixture was treated with excess celite and filtered to remove solids. The organic layer was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (10% EtOAc/Hex) gave 409 mg (17%). 1H NMR (CDCl3) δ: 8.16-8.22 (m, 1H), 8.13 (dd, J=8.2, 2.4 Hz, 1H), 7.29-7.39 (m, 2H), 7.06-7.20 (m, 2H), 6.97-7.06 (m, 1H). 19F NMR (CDCl3) δ: −74.07 (d, J=8.7 Hz, 1F), −118.78 (d, J=8.7 Hz, 1F), −123.39 (br. s., 1F). Mass spec.: 314.1 (MH)+.
Reaction SMILES: C(O[C@H](C)[C@H](NC(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)C(O)=O)C1C=CC=CC=1.N[C@H](C1C=CC(OC[C@H](O)CO)=CC=1)C(N[C@@H]([C@H](C1C=CC=CC=1)C)C(NC1C=CC(I)=CC=1Cl)=O)=O.N[C@H](C1C=CC(OC[C@H](O[Si](C)(C)C)CO[Si](C)(C)C)=CC=1)C(N[C@@H]([C@H](C1C=CC=CC=1)C)C(NC1C=CC(I)=CC=1Cl)=O)=O.C(OC(N[C@H](C1C=CC(OC[C@H]2COC(C)(C)O2)=CC=1)C(O)=O)=O)(C)(C)C.C[Si](C)(C)[O:144][C@H:145]([CH2:181][O:182][Si](C)(C)C)[CH2:146][O:147][C:148]1[CH:153]=[CH:152][C:151]([C@@H:154]2[C:158](=[O:159])[N:157]([C@@H:160]([C@H:172]([C:174]3[CH:179]=[CH:178][CH:177]=[CH:176][CH:175]=3)[CH3:173])[C:161]([NH:163][C:164]3[CH:169]=[CH:168][C:167]([I:170])=[CH:166][C:165]=3[Cl:171])=[O:162])[C:156](=[O:180])[NH:155]2)=[CH:150][CH:149]=1>>[Cl:171][C:165]1[CH:166]=[C:167]([I:170])[CH:168]=[CH:169][C:164]=1[NH:163][C:161](=[O:162])[C@@H:160]([N:157]1[C:158](=[O:159])[C@@H:154]([C:151]2[CH:150]=[CH:149][C:148]([O:147][CH2:146][C@H:145]([OH:144])[CH2:181][OH:182])=[CH:153][CH:152]=2)[NH:155][C:156]1=[O:180])[C@H:172]([C:174]1[CH:175]=[CH:176][CH:177]=[CH:178][CH:179]=1)[CH3:173]
Reactant: C[C@@H](c1ccccc1)[C@@H](C(=O)Nc1ccc(I)cc1Cl)N1C(=O)N[C@H](c2ccc(OC[C@@H](CO[Si](C)(C)C)O[Si](C)(C)C)cc2)C1=O
Agent: CC(C)(C)OC(=O)N[C@@H](C(=O)O)c1ccc(OC[C@H]2COC(C)(C)O2)cc1
Agent: C[C@@H](OCc1ccccc1)[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: C[C@@H](c1ccccc1)[C@H](NC(=O)[C@H](N)c1ccc(OC[C@@H](CO[Si](C)(C)C)O[Si](C)(C)C)cc1)C(=O)Nc1ccc(I)cc1Cl
Product: C[C@@H](c1ccccc1)[C@@H](C(=O)Nc1ccc(I)cc1Cl)N1C(=O)N[C@H](c2ccc(OC[C@H](O)CO)cc2)C1=O

Procedure:
Prepared by the same method as described in example 110 except that (i) (R)-tert-butoxycarbonylamino-[4-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-acetic acid (prepared as described below) was used in place of (R)-tert-butoxycarbonylamino-{4-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-acetic acid in step 4, (ii) (2S,3S)-2-{(R)-2-amino-2-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide was temporarily protected as (2S,3S)-2-{(R)-2-amino-2-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-acetylamino}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide (performed as described below) prior to performing step 6, and (iii) acid catalyzed hydrolysis of (2S,3S)-2-{(R)-4-[4-((S)-2,3-bis-trimethylsilanyloxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-N-(2-chloro-4-iodo-phenyl)-3-phenyl-butyramide (performed as described below) was performed prior to purification and isolation of (2S,3S)—N-(2-chloro-4-iodo-phenyl)-2-{(R)-4-[4-((R)-2,3-dihydroxy-propoxy)-phenyl]-2,5-dioxo-imidazolidin-1-yl}-3-phenyl-butyramide in step 6.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18]C)=[CH:14][CH:13]=2)[CH:3]=1.B(Br)(Br)Br>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[CH:3]=1
Reactant: COc1ccc(Nc2cc(Cl)ccc2C(=O)O)cc1
Agent: BrB(Br)Br
Product: O=C(O)c1ccc(Cl)cc1Nc1ccc(O)cc1

Procedure:
4-Chloro-2-(4-hydroxyphenylamino)benzoic acid [XI; R=4Cl, R"=H, OH at 4-position] was prepared by reaction of 4-chloro-2-(4-methoxyphenylamino)benzoic acid with boron tribromide according to the procedure of Example 3, part (b), and obtained as a gray solid, m.p. 164°-165° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[C:14]2[CH:13]=[C:12]3[NH:15][C:16]4[C:21]([C:11]3=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:20][N:19]=[CH:18][CH:17]=4.[H-].[Na+].Cl[C:26]1[N:31]=[C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[N:29]=[C:28]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[N:27]=1>CN(C)C=O.C1COCC1>[C:38]1([C:28]2[N:29]=[C:30]([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:31]=[C:26]([N:15]3[C:12]4=[CH:13][C:14]5[C:2]([CH3:22])([CH3:1])[C:3]6[C:8]([C:9]=5[CH:10]=[C:11]4[C:21]4[C:16]3=[CH:17][CH:18]=[N:19][CH:20]=4)=[CH:7][CH:6]=[CH:5][CH:4]=6)[N:27]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1
Reactant: Clc1nc(-c2ccccc2)nc(-c2ccccc2)n1
Reactant: CC1(C)c2ccccc2-c2cc3c(cc21)[nH]c1ccncc13
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC1(C)c2ccccc2-c2cc3c4cnccc4n(-c4nc(-c5ccccc5)nc(-c5ccccc5)n4)c3cc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
10 g (35.17 mmol) of 10,10-dimethyl-10,12-dihydro-3,12-diazaindeno-[2,1-b]fluorene are dissolved in 150 ml of dimethylformamide under a protective-gas atmosphere, and 1.7 g of 60% NaH in mineral oil (42.2 mmol) are added. After 1 h at room temperature, a solution of 2-chloro-4,6-diphenyl-1,3,5-triazine (10.7 g, 38.68 mmol) in 100 ml of THF is added dropwise. The reaction mixture is stirred at room temperature for 12 h. After this time, the reaction mixture is poured onto ice and extracted three times with dichloromethane. The combined organic phases are dried over Na2SO4 and evaporated. The residue is extracted with hot toluene, recrystallised from toluene and finally sublimed in a high vacuum, the purity is 99.9%. The yield is 14.4 g (80%).
Reaction SMILES: [NH2:1][CH:2]([C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4].[C:14]([C:18]1[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=1)([CH3:17])([CH3:16])[CH3:15].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:13][C:10]1[CH:9]=[CH:8][C:7]([CH:2]([NH:1][C:22](=[O:23])[C:21]2[CH:25]=[CH:26][C:18]([C:14]([CH3:16])([CH3:15])[CH3:17])=[CH:19][CH:20]=2)[C:3]([O:5][CH3:6])=[O:4])=[CH:12][CH:11]=1
Reactant: COC(=O)C(N)c1ccc(Br)cc1
Reactant: CC(C)(C)c1ccc(C(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)C(NC(=O)c1ccc(C(C)(C)C)cc1)c1ccc(Br)cc1
Reaction time: 4 h
Yield: 87.7 %

Procedure:
Prepared using General Procedure 7. To a stirring solution of methyl 2-amino-2-(4-bromophenyl)acetate (421 mg, 1.5 mmol), 4-(tert-butyl)benzoic acid (321 mg, 1.8 mmol), and DIEA (831 μl, 4.5 mmol) in DMF (3 mL) cooled to 0° C. was slowly added a solution of HATU (380 mg, 1.65 mmol) in DMF (1.5 mL) in a drop-wise fashion. The reaction mixture was allowed to warm slowly and stirring continued for 4 h. The reaction mixture was poured onto ice-water and the solid was filtered. The solid was dissolved in DCM (10 mL), dried over MgSO4 and evaporated to afford 532 mg (88%) of methyl 2-(4-bromophenyl)-2-(4-(tert-butyl)benzamido)acetate. LCMS-ESI (m/z) calculated for C20H22BrNO3: 403.0. found 404.1 [M+H]+, tR=3.61 min. (Method 16).
Reaction SMILES: [NH2:1][C:2]1[C:19]([Cl:20])=[CH:18][C:5]([C:6]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=2)=[CH:7][C:8]([OH:10])=O)=[CH:4][C:3]=1[Cl:21].ClC(OCC)=O.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>C(N(CC)CC)C>[NH2:1][C:2]1[C:3]([Cl:21])=[CH:4][C:5]([C:6]([C:11]2[CH:16]=[CH:15][C:14]([Br:17])=[CH:13][CH:12]=2)=[CH:7][C:8]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)=[O:10])=[CH:18][C:19]=1[Cl:20]
Reactant: C1COCCN1
Reactant: Nc1c(Cl)cc(C(=CC(=O)O)c2ccc(Br)cc2)cc1Cl
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Product: Nc1c(Cl)cc(C(=CC(=O)N2CCOCC2)c2ccc(Br)cc2)cc1Cl

Procedure:
This compound was prepared from 4-amino-β-(4'-bromophenyl)-3,5-dichloro-cinnamic acid (isomer ratio A:B=1:2.5), ethyl chloroformate, triethylamine and morpholine analogous to Example 1(c).
Reaction SMILES: [CH2:1]([NH:3][C:4](=[O:36])[NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]3[CH3:35])[C:15]3[CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18][C:16]=3[N:17]=2)=[CH:8][CH:7]=1)C.CNC(NC1C=CC(B2OC(C)(C)C(C)(C)O2)=CC=1)=O.ClC1N=C(N2CCOC[C@@H]2C)C2CCN(C(OC(C)(C)C)=O)CC=2N=1>>[CH3:1][NH:3][C:4]([NH:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:13]=[C:14]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]3[CH3:35])[C:15]3[CH2:21][CH2:20][NH:19][CH2:18][C:16]=3[N:17]=2)=[CH:10][CH:11]=1)=[O:36]
Reactant: CCNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CCN(C(=O)OC(C)(C)C)C3)cc1
Agent: CNC(=O)Nc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Agent: C[C@H]1COCCN1c1nc(Cl)nc2c1CCN(C(=O)OC(C)(C)C)C2
Product: CNC(=O)Nc1ccc(-c2nc3c(c(N4CCOC[C@@H]4C)n2)CCNC3)cc1

Procedure:
Method as described for intermediate 5 using 1-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea and intermediate 4 as starting materials. Followed by method as described for example 3 step 2.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=O)C.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1>[OH:3][CH2:4][C:6]1[N:7]([S:15]([C:18]2[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=2)(=[O:17])=[O:16])[C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2
Reactant: CCOC(=O)c1cc2ccccc2n1S(=O)(=O)c1ccc(C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2c(CO)cc3ccccc32)cc1
Temperature: 5 °C
Reaction time: 1 h
Yield: 99.1 %

Procedure:
To stirred solution of Red-A1 (sodium dihydro-bis(2-methoxyethoxy)aluminate ≈70% in toluene) (30 mL) in dry THF (100 mL) cooled at 5° C. and under nitrogen was added dropwise and at this temperature a solution of compound of step 1 (26,8 g, 78 mmol) in dry THF (75 mL). After stirring one hour at 5° C. and then one hour at room temperature the mixture was cooled at 10° C. and treated dropwise with 2N NaOH, to effect hydrolysis of the intermediate complex. The organic phase was separated and the solvent in vacuo evaporated. The residue was solved in ethyl ether, the solution washed with water, dried over MgSO4 and evaporated to give the required alcohol (23.3 g, 98%) as a yellow oil; IR (film) 3500, 1597 cm-1.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].Cl.[Cl:10][CH2:11][C:12](=N)OCC>C(O)C>[Cl:10][CH2:11][C:12]1[O:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[N:1]=1
Reactant: Nc1ccccc1O
Reactant: CCOC(=N)CCl
Agent: Cl
Solvent: CCO
Product: ClCc1nc2ccccc2o1
Temperature: 25 °C
Yield: 65 %

Procedure:
A mixture of o-aminophenol (4.00 g, 36.6 mmol) and ethyl chloroacetimidate hydrochloride (8.68 g, 54.98 mmol) in ethanol (55 mL) was heated at reflux for 18 hours. The reaction mixture was cooled to room temperature and vacuum filtered. The filtrate was concentrated in vacuo, diluted with methylene chloride and filtered again. The methylene chloride filtrate was dried (MgSO4) and concentrated to afford 3.99 g (65%) of product as a brown oil which was used directly in the next step.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[C@H:20]([CH3:21])[O:19][CH:6](OC(=O)C2C=CC([N+]([O-])=O)=CC=2)[CH2:5][C@H:4]1[NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25].[ClH:29]>C(Cl)Cl>[CH3:1][O:2][C@@H:3]1[C@@H:20]([CH3:21])[O:19][CH:6]([Cl:29])[CH2:5][C@@H:4]1[NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25]
Reactant: Cl
Reactant: CO[C@H]1[C@H](C)OC(OC(=O)c2ccc([N+](=O)[O-])cc2)C[C@H]1NC(=O)C(F)(F)F
Solvent: ClCCl
Product: CO[C@H]1[C@@H](NC(=O)C(F)(F)F)CC(Cl)O[C@@H]1C
Yield: 100 %

Procedure:
A solution of 1.76 g; 4.34 mmol of compound VIII in 48 ml of anhydrous methylene dichloride was saturated at 0° C. with anhydrous hydrogen chloride. The resulting precipitate of p-nitrobenzoic acid was filtered off under anhydrous conditions and the filtrate was evaporated to give a residue of 1.2 g (yield 100%) of 4-O-methyl-2,3,6-trideoxy-3-trifluoroacetamido-L-ribohexopyranosyl chloride (III).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([OH:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].O.[C:15](#[N:18])[CH:16]=[CH2:17]>C(O)(=O)C>[C:15]([CH2:16][CH2:17][S:11]([C:8]1[CH:7]=[CH:6][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:10][CH:9]=1)(=[O:13])=[O:12])#[N:18]
Reactant: C=CC#N
Reactant: CC(=O)Nc1ccc(S(=O)O)cc1
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)Nc1ccc(S(=O)(=O)CCC#N)cc1
Temperature: 25 °C
Yield: 67.8 %

Procedure:
A solution of 19.9 g (0.1 mol) of p-acetamidobenzenesulfinic acid (Organic Synthesis, Coll. Vol. I, page 7), 100 ml of water, 40 ml of acetic acid and 6.6 ml (0.1 mole) of acrylonitrile was heated on a steam bath for 2 hours. The resulting slurry was cooled to room temperature, filtered, washed with water and air dried to give 17.1 g (68 percent) of white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.CC(C)([O-])C.[K+].[Si:18]([O:25][CH2:26][CH2:27][OH:28])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]>C1COCC1>[C:21]([Si:18]([O:25][CH2:26][CH2:27][O:28][C:7]1[CH:6]=[CH:5][C:4]([N+:9]([O-:11])=[O:10])=[CH:3][C:2]=1[F:1])([CH3:20])[CH3:19])([CH3:24])([CH3:23])[CH3:22]
Reactant: CC(C)(C)[Si](C)(C)OCCO
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCCOc1ccc([N+](=O)[O-])cc1F
Yield: 102.1 %

Procedure:
The same procedure detailed below for Compound 133 was used, but using 3,4-difluoronitrobenzene (225 mg, 1.4 mmol), potassium tert-butoxide (354 mg, 3.2 mmol) and 2-((tert-butyldimethylsilyl)oxy)ethan-1-ol (506 mg, 2.9 mmol) in THF (3 mL) to give the product (451 mg) after workup (yield assumed quantitative). The product was used in the next step without further purification.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:13][C:12]([C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=3)([C:14]([F:17])([F:16])[F:15])[O:11][N:10]=2)=[CH:5][CH:4]=1.[C:26]1(=[O:36])[NH:30][C:29](=[O:31])[C:28]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]12.[K]>CN(C)C=O.C(OCC)(=O)C>[Cl:25][C:20]1[CH:19]=[C:18]([C:12]2([C:14]([F:17])([F:15])[F:16])[O:11][N:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([CH2:2][N:30]4[C:29](=[O:31])[C:28]5=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]5[C:26]4=[O:36])=[CH:8][CH:7]=3)[CH2:13]2)[CH:23]=[C:22]([Cl:24])[CH:21]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: FC(F)(F)C1(c2cc(Cl)cc(Cl)c2)CC(c2ccc(CCl)cc2)=NO1
Agent: [K]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1Cc1ccc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 99.6 %

Procedure:
In a solution of 1.20 g of 3-[4-(chloromethyl)phenyl]-5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole in 20 mL of N,N-dimethylformamide, 0.54 g of potassium phthalimide was added and stirred at room temperature for 20 hours. After the completion of the reaction, the reaction mixture was diluted with 100 mL of ethyl acetate, washed with water (50 mL×3) and then dehydrated with and dried over saturated sodium chloride aqueous solution and anhydrous magnesium sulfate in that order, and the solvent was distilled off under reduced pressure to obtain 1.50 g of the aimed product as white crystal.