Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22]O)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]
Reactant: CC(C)(C)OC(=O)N1CCC(CO)CC1
Reactant: Fc1ccccc1S
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(CSc2ccccc2F)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 4.8 %

Procedure:
After dissolving 1.97 g of 2-fluorothiophenol in 50 ml of tetrahydrofuran, 3.0 g of 1-(tert-butoxycarbonyl)piperidine-4-methanol and 4.03 g of triphenylphosphine were added, and then 3.3 ml of diethyl azodicarboxylate was added dropwise while cooling on ice and the mixture was stirred overnight at room temperature. The reaction solution was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (216 mg, 5% yield).
Reaction SMILES: [N:1]1([C:7]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][C:8]=2[C:9](Cl)=[O:10])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Cl.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH2:28][CH2:29][NH:30][CH2:31][CH:32]=2)=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH2:32][CH2:31][N:30]([C:9]([C:8]3[CH:12]=[C:13]([N+:16]([O-:18])=[O:17])[CH:14]=[CH:15][C:7]=3[N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:10])[CH2:29][CH:28]=2)=[CH:23][CH:22]=1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])ccc1N1CCOCC1
Reactant: Clc1ccc(C2=CCNCC2)cc1
Agent: Cl
Product: O=C(c1cc([N+](=O)[O-])ccc1N1CCOCC1)N1CC=C(c2ccc(Cl)cc2)CC1

Procedure:
According to the procedure described for the synthesis of example 1, the title compound has been synthesized from 2-morpholin-4-yl-5-nitro-benzoyl chloride and 4-(4-Chloro-phenyl)-1,2,3,6-tetrahydro-pyridine hydrochloride (commercial). MS (m/e): 428.1 (MH+, 100%)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:12]O)[CH:6]=[CH:7][C:8]=1[N+:9]([O-:11])=[O:10].S(Cl)([Cl:16])=O>>[Cl:16][CH2:12][C:5]1[CH:6]=[CH:7][C:8]([N+:9]([O-:11])=[O:10])=[C:3]([O:2][CH3:1])[CH:4]=1
Reactant: COc1cc(CO)ccc1[N+](=O)[O-]
Reactant: O=S(Cl)Cl
Product: COc1cc(CCl)ccc1[N+](=O)[O-]
Yield: 99.9 %

Procedure:
A mixture of (3-methoxy-4-nitrophenyl)methanol (0.5 g, 2.73 mmol) and thionyl chloride (0.3 mL, 4.09 mmol) was heated at reflux for 12 h. then the mixture concentrated in vacuo to afford 0.55 g of 4-(chloromethyl)-2-methoxy-1-nitrobenzene, (yield: 100% yield) which was used in further chemistries without purification.
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=O)=[CH:10][C:5]=2[N:4]=[CH:3]1.[CH2:14]1[C@H:23]2[C@H:18]([CH2:19][CH2:20][C:21]3[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=32)[NH:17][CH2:16][CH2:15]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>>[CH2:14]1[C@H:23]2[C@H:18]([CH2:19][CH2:20][C:21]3[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=32)[N:17]([C:11]([C:9]2[CH:8]=[CH:7][C:6]3[N:2]([CH3:1])[CH:3]=[N:4][C:5]=3[CH:10]=2)=[O:13])[CH2:16][CH2:15]1
Reactant: c1ccc2c(c1)CC[C@@H]1NCCC[C@H]21
Reactant: Cn1cnc2cc(C(=O)O)ccc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: Cn1cnc2cc(C(=O)N3CCC[C@@H]4c5ccccc5CC[C@@H]43)ccc21
Yield: 83 %

Procedure:
The title compound is prepared from 1-methyl-1H-benzoimidazole-5-carboxylic acid and cis-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline following a procedure analogous to that described in Example 1 [2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexa-fluorophosphate is used]. Yield: 83% of theory; LC (method 5): tR=1.05 min; Mass spectrum (ESI+): m/z=346 [M+H]+.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]1[CH:13]([CH:14]=[CH:15][C:16](=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:12][CH:11]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH:10]1[OH:30].S(=O)(=O)(O)[OH:32].C(OCC)C.O>CN(C)C=O.[O-2].[O-2].[O-2].[Cr+6]>[O:30]=[C:10]1[CH:11]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH2:12][CH:13]([CH:14]=[CH:15][C:16](=[O:22])[CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH:9]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][C:2]([OH:32])=[O:1]
Reactant: O=S(=O)(O)O
Reactant: CCCCCC(=O)C=CC1CC(OC2CCCCO2)C(O)C1CCCCCCCO
Agent: [Cr+6]
Agent: [O-2]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCC(=O)C=CC1CC(OC2CCCCO2)C(=O)C1CCCCCCC(=O)O
Reaction time: 1.5 h

Procedure:
Chromium trioxide (4.0 g.) (dried over phosphorus pentoxide) was added portionwise to a stirred solution of 2-(7-hydroxyheptyl)-3-(3-oxooct-1-enyl)-5-(2-tetrahydropyranyloxy)cyclopentanol [2.12 g., prepared as described in Example 2(f)] in dry dimethylformamide (30 ml.), while maintaining the temperature at between 5° and 15° C. A solution of concentrated sulphuric acid (1.4 ml.) in dimethylformamide (40 ml.) was then added and the mixture was stirred at between 5° and 15° C. for a further 90 minutes. Diethyl ether was then added, followed by a minimum quantity of water to produce two readily separable layers. The ethereal layer was separated and stirred with an aqueous 2N sodium carbonate solution. This aqueous layer was then separated, washed with diethyl ether, and then treated with a further quantity of diethyl ether and acidified to pH 4 by the dropwise addition of concentrated hydrochloric acid. The resulting ethereal layer was separated, and the remaining aqueous layer was extracted with a further quantity of diethyl ether. These last two ethereal solutions were then combined, dried over magnesium sulphate, and evaporated to dryness, to give crude 7-(2-oxo-5-(3-oxooct-1-enyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid (1.03 g.), νmax 1720 cm-1, 1700 cm-1, 1670 cm-1, 1625 cm-1, 985 cm-1, which was used as starting material in the following preparation (h) of 7-[2-hydroxy-5-(3-hydroxyoct-1-enyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanoic acid, without further purification being necessary.
Reaction SMILES: COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]5[C:28](=[O:40])[N:29]([C:33]6[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=6)[N:30]=[CH:31][CH:32]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([N:42]3[CH2:48][CH2:47][CH2:46][NH:45][CH2:44][CH2:43]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[N:42]1([C:10]2[C:11]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[O:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]4[C:28](=[O:40])[N:29]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[N:30]=[CH:31][CH:32]=4)=[O:26])=[CH:20][C:19]=3[F:41])[NH:8][N:9]=2)[CH2:48][CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1
Reactant: COc1ccc(Cn2nc(N3CCCNCC3)c3c(Oc4ccc(NC(=O)c5ccnn(-c6ccc(F)cc6)c5=O)cc4F)ccnc32)cc1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1ccc(Oc2ccnc3[nH]nc(N4CCCNCC4)c23)c(F)c1)c1ccnn(-c2ccc(F)cc2)c1=O
Temperature: 80 °C
Reaction time: 8 h
Yield: 1.8 %

Procedure:
A 100 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(1,4-diazepan-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (60.7 mg, 0.0894 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 80° C. overnight. The solvent was removed and the residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product, which was further purified by preparative HPLC to afford the product (0.9 mg, 1.28%). LRMS (APCI pos): >99% purity, 254 nm, m/e 559 (M+1). 1H NMR (400 MHz, CD3OD δ 8.34 (m, 2H), 8.22 (d, 1H), 8.07 (d, 1H), 7.67 (m, 2H), 7.52 (d, 1H), 7.43 (t, 1H), 7.30 (m, 2H), 6.27 (d, 1H), 3.91 (m, 2H), 3.75 (m, 2H), 3.48 (m, 2H), 3.39 (m, 2H), 2.23 (m, 2H).
Reaction SMILES: [F-:1].[K+].C1N2CCOCCOCCN(CCOCCOCC2)CCOCCOC1.CS([O:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([CH:41]=O)=[CH:37][CH:36]=1)(=O)=O>C(#N)C>[F:1][CH2:41][C:38]1[CH:39]=[CH:40][C:35]([CH:34]=[O:33])=[CH:36][CH:37]=1
Reactant: [F-]
Reactant: CS(=O)(=O)OCc1ccc(C=O)cc1
Agent: C1COCCN2CCOCCOCCN(CCO1)CCOCCOCC2
Agent: [K+]
Solvent: CC#N
Product: O=Cc1ccc(CF)cc1
Reaction time: 0.17 h

Procedure:
KF (2.7 mg, 0.047 mmol) and kryptofix 222 (17.6 mg, 0.047 mmol) were dissolved in acetonitrile (1 ml) and added to (4-formylphenyl)methyl methanesulfonate (10 mg, 0.047 mmol) in acetonitrile (1 ml). The reaction mixture was heated to 65 degrees for 10 minutes. The crude product was purified using a silica short column and diethyl ether. (Analytical HPLC: column Phenomenex Luna 00B-4251-E0, solvents: A=water/0.1% TFA and B=CH3CN/0.1% TFA; gradient 5-50% B over 10 min; flow 2.0 ml/minute; retention time 5.1 minutes detected at 214 and 254 nm).
Reaction SMILES: C[SiH](C)C1C=CC=CC=1[SiH](C)C.[CH3:13][N:14]([CH3:24])[C:15](=O)[C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[CH3:24][N:14]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([Br:22])=[CH:20][CH:21]=1)[CH3:13]
Reactant: CN(C)C(=O)c1ccc(Br)cc1
Agent: C[SiH](C)c1ccccc1[SiH](C)C
Solvent: Cc1ccccc1
Product: CN(C)Cc1ccc(Br)cc1
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 86 %

Procedure:
A 20-mL eggplant flask equipped with a three-way cock and a magnetic stirrer was heat dried while pumping to a vacuum of 5 Pa before its interior was purged with argon atmosphere. Into the flask, iron complex A (1.0 mg, 0.002 mmol) was admitted as catalyst and dissolved in toluene (0.5 mL). To the solution, 1,2-bis(dimethylsilyl)benzene (475 μL) was added through a syringe, and N,N-dimethyl-4-bromobenzamide (228 mg, 1.0 mmol) was added. The solution was stirred at 100° C. for 30 minutes. Toluene was distilled off in vacuum. The crude product was purified by silica gel-packed column chromatography using hexane/ethyl acetate (20/1) as developing solvent, obtaining N,N-dimethyl-4-bromobenzylamine (184 mg, 0.86 mmol, 86%). The results are shown as Entry 2 in Table 5. The resulting amine was identified for geometry by 1H and 13C-NMR spectroscopy and IR spectroscopy.
Reaction SMILES: [NH2:1][CH:2]1[CH:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:18][CH2:19][CH2:20][NH:21][S:22]([C:25]3[N:26]=[CH:27][N:28]([CH3:30])[CH:29]=3)(=[O:24])=[O:23])[CH:8]=2)[CH2:3]1.Br[CH2:32][CH:33]([CH3:36])[CH2:34]Cl.C(=O)([O-])[O-].[K+].[K+].C(#N)C>O.ClCCl>[CH2:11]([CH:10]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:18][CH2:19][CH2:20][NH:21][S:22]([C:25]3[N:26]=[CH:27][N:28]([CH3:30])[CH:29]=3)(=[O:24])=[O:23])[CH:8]=2)[CH2:3][CH:2]1[N:1]1[CH2:34][CH:33]([CH3:36])[CH2:32]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Cn1cnc(S(=O)(=O)NCCOc2ccc3c(c2)C(Cc2ccccc2)C(N)C3)c1
Reactant: CC(CCl)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Solvent: ClCCl
Product: CC1CN(C2Cc3ccc(OCCNS(=O)(=O)c4cn(C)cn4)cc3C2Cc2ccccc2)C1
Reaction time: 0.67 h

Procedure:
To N-(2-(2-amino-3-benzyl-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide (43 mg, 0.101 mmol; see example 193), 1-bromo-3-chloro-2-methylpropane (0.093 mL, 0.807 mmol) and potassium carbonate (111 mg, 0.807 mmol) in water (1 mL) +1 drop acetonitrile were added. Microwave at 120° C. for 40 min. Evaporated acetonitrile, re-dissolved in dichloromethane and extracted with water and brine, dried over sodium bicarbonate, filtered and evaporated to obtain the crude product as a brown oil, that was purified by flash silica gel chromatography on 4 g SiO2-cartridge using 10% methanol in dichloromethane to afford N-(2-(3-benzyl-2-(3-methylazetidin-1-yl)-2,3-dihydro-1H-inden-5-yloxy)ethyl)-1-methyl-1H-imidazole-4-sulfonamide as a yellow oil. m=4.9 mg (10%)
Reaction SMILES: [S:1]1[CH:5]=[C:4]([CH2:6][C:7](Cl)=[O:8])[S:3][C:2]1=[O:10].[NH2:11][CH:12]1[C:19](=[O:20])[N:18]2[CH:13]1[S:14][CH2:15][C:16]([CH3:29])=[C:17]2[C:21]([O:23]CC(Cl)(Cl)Cl)=[O:22].C(N(CC)CC)C>C(Cl)(Cl)Cl.C(OCC)(=O)C>[C:21]([C:17]1[N:18]2[CH:13]([S:14][CH2:15][C:16]=1[CH3:29])[CH:12]([NH:11][C:7](=[O:8])[CH2:6][C:4]1[S:3][C:2](=[O:10])[S:1][CH:5]=1)[C:19]2=[O:20])([OH:23])=[O:22]
Reactant: O=C(Cl)Cc1csc(=O)s1
Reactant: CC1=C(C(=O)OCC(Cl)(Cl)Cl)N2C(=O)C(N)C2SC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: CC1=C(C(=O)O)N2C(=O)C(NC(=O)Cc3csc(=O)s3)C2SC1
Temperature: -10 °C
Reaction time: 24 h
Yield: 14.1 %

Procedure:
A solution of (1,3-dithiol-2-on-4-yl)-acetyl chloride (13.2 g.) in chloroform (110 cc.) is added to a solution of 7-amino-3-methyl-8-oxo-2-(2,2,2-trichloroethoxycarbonyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (23 g.) and triethylamine (9.5 cc.) in chloroform (300 cc.), maintained at -10° C., over the course of one hour. The reagents are left in contact for 24 hours at a temperature of between 0° and 10° C., and the chloroform is then driven off under reduced pressure (20 mm.Hg). The residue is taken up in ethyl acetate (one liter) and the solution is washed first with an 0.1 N hydrochloric acid solution (250 cc.), then with a saturated aqueous sodium bicarbonate solution (250 cc.) and finally twice with water (250 cc.). The organic phase is dried over magnesium sulphate, treated with decolourising charcoal and filtered. The filtrate is concentrated under reduced pressure (20 mm.Hg) to a volume of 100 cc. and then added to isopropyl ether (one liter). The product, 3-methyl-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-2-(2,2,2-trichloroethoxycarbonyl)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene (27 g.) precipitates and is filtered off. This product (17 g.) is dissolved in dimethylformamide (120 cc.) and acetic acid (35 cc.). The mixture is cooled in an ice bath, zinc powder (20.8 g.) is added and the mixture is stirred for 31/2 hours. The reaction mixture is then filtered; ethyl acetate (400 cc.) is added to the filtrate and the mixture is washed twice with water (a total of 400 cc.). The organic phase is extracted three times with a saturated sodium bicarbonate solution (200 cc.). The alkaline solution is acidified to pH 2.5 by adding 4 N hydrochloric acid in the presence of ethyl acetate (400 cc.). After decanting the organic phase, the aqueous phase is extracted twice with ethyl acetate (a total of 200 cc.); the organic extracts are combined, washed twice with water (a total of 200 cc.), dried over magnesium sulphate, treated with decolourising charcoal and filtered. The filtrate is concentrated to dryness under reduced pressure (20 mm.Hg). The residue obtained is recrystallised from a mixture of acetone and petroleum ether (100 cc.) to give 2-carboxy-3-methyl-8-oxo-7-[(1,3-dithiol-2-on-4-yl)-acetamido]-5-thia-1-aza-bicyclo[4.2.0]-oct-2-ene (3.5 g.).
Reaction SMILES: [OH:1][CH:2]([C:17]1[N:18]=[CH:19][N:20]([C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:21]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([NH:15][CH3:16])=[O:14])[CH:7]=[CH:6]2.CN(C)C(=O)C.[H-].[Na+].Cl>O>[CH3:16][NH:15][C:13]([C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:2]([C:17]3[N:18]=[CH:19][N:20]([C:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH:21]=3)=[O:1])[CH:4]=2)[CH:9]=1)=[O:14]
Reactant: CNC(=O)c1ccc2cc(C(O)c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: CNC(=O)c1ccc2cc(C(=O)c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2c1
Temperature: 0 °C
Reaction time: 60 h
Yield: 89.5 %

Procedure:
Under a nitrogen atmosphere, 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (1.0 g, 1.91 mmol) was added to N,N-dimethylacetamide (50 mL), and then sodium hydride (oil, 0.15 g, 3.85 mmol) was added at room temperature, and the mixture was stirred at the same temperature for about 60 hr. To the reaction mixture were added dropwise water (50 mL) and 1 mol/L hydrochloric acid (5 mL) at room temperature, and the mixture was stirred at the same temperature for 45 min. Then, the reaction mixture was cooled to 0° C., and stirred for 2 hr. The crystals were collected by filtration, and washed with water (30 mL). The obtained wet crystals were dried under reduced pressure to give N-methyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide (0.89 g, 1.71 mmol). yield 90%.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[N:6]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@@H:5]([CH2:14][C@H:15]2[CH2:21][CH:20]=[CH:19][CH2:18][O:17][CH2:16]2)[CH2:4][O:3]1>CCO.[Ni]>[CH3:1][C:2]1([CH3:22])[N:6]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@@H:5]([CH2:14][C@H:15]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17][CH2:16]2)[CH2:4][O:3]1
Reactant: CC(C)(C)OC(=O)N1[C@@H](C[C@H]2CC=CCOC2)COC1(C)C
Agent: [Ni]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1[C@@H](C[C@H]2CCCCOC2)COC1(C)C
Reaction time: 3 h
Yield: 72 %

Procedure:
The (S)-tert-butyl 2,2-dimethyl-4-(((R,Z)-2,3,4,7-tetrahydrooxepin-3-yl)methyl)oxazolidine-3-carboxylate was dissolved in EtOH, followed by the addition of Raney Ni. The mixture was hydrogenated at rt for 3 h. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to afford (S)-tert-butyl 2,2-dimethyl-4-((R)-oxepan-3-ylmethyl)oxazolidine-3-carboxylate (408 mg, 72%).
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:5]2[CH2:10][N:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][C:6]=2[N:7]=1.[CH:22]1([NH:25][C:26]([NH:28][C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[C:31]([F:44])[CH:30]=2)=[O:27])[CH2:24][CH2:23]1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].CCO.O.COCCOC>[CH:22]1([NH:25][C:26](=[O:27])[NH:28][C:29]2[CH:34]=[CH:33][C:32]([C:2]3[N:3]=[C:4]([N:16]4[CH2:21][CH2:20][O:19][CH2:18][CH2:17]4)[C:5]4[CH2:10][N:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:8][C:6]=4[N:7]=3)=[C:31]([F:44])[CH:30]=2)[CH2:23][CH2:24]1
Reactant: CCOC(=O)N1Cc2nc(Cl)nc(N3CCOCC3)c2C1
Reactant: CC1(C)OB(c2ccc(NC(=O)NC3CC3)cc2F)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)N1Cc2nc(-c3ccc(NC(=O)NC4CC4)cc3F)nc(N3CCOCC3)c2C1
Yield: 3.4 %

Procedure:
A solution of ethyl 2-chloro-4-morpholino-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (intermediate 27) (156 mg, 0.498 mmol), 1-cyclopropyl-3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (intermediate 29) (182 mg, 0.567 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II), complex with dichloromethane (20 mg, 0.0249 mmol) and sodium carbonate (148 mg, 1.39 mmol) in 2 ml of a 7:3:1 mixture of DME:H2O:EtOH respectively was heated in the microwave at 115° C. for 45 minutes. The reaction was concentrated in vacuo and the residue redissolved in a mix of MeOH/DCM. It was loaded onto an SCX cartridge and washed with two column volumes of MeOH/DCM before being eluted with 2M NH3 in MeOH and concentrated in vacuo to give a solid which was then triturated in MeOH to yield the title compound (8 mg, 3%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[O:19][CH3:20])[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([F:15])[CH:9]=1)=[O:6].[Cl:21][C:22]1[CH:23]=[C:24]([S:29](Cl)(=[O:31])=[O:30])[CH:25]=[C:26]([Cl:28])[CH:27]=1>N1C=CC=CC=1>[Cl:28][C:26]1[CH:25]=[C:24]([S:29]([NH:1][C:2]2[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[C:10]([F:15])[CH:9]=2)=[O:6])(=[O:30])=[O:31])[CH:23]=[C:22]([Cl:21])[CH:27]=1
Reactant: COc1ccc(C(=O)Nc2ccc(F)c(F)c2)cc1N
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1
Solvent: c1ccncc1
Product: COc1ccc(C(=O)Nc2ccc(F)c(F)c2)cc1NS(=O)(=O)c1cc(Cl)cc(Cl)c1
Reaction time: 16 h
Yield: 94.4 %

Procedure:
A solution of 3-amino-4-methoxy-N-(3,4-difluorophenyl)-benzamide from Example 15 (0.834 g, 3.00 mmol), 3,5-dichlorobenzenesulfonyl chloride (0.736 g, 3.00 mmol) and a catalytic amount of 4-dimethylaaminopyridine in pyridine (10 mL) was stirred under nitrogen at room temperature. After 16 hours, the solvent was removed in vacuo and the residue shaken with a mixture of ethyl acetate and 1N HCl then filtered. The layers were separated and the organic layer washed with brine, dried with MgSO4, concentrated to dryness, triturated in hexanes and filtered to afford a solid which was combined with that obtained in the filtration step to afford the product (1.38 g); m.p. 228-231° C.
Reaction SMILES: [C:1]1([NH:7][C:8](=[O:19])[C:9]2[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=2[F:18])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[N+:15]([C:13]1[CH:14]=[C:9]([C:8]2[O:19][C:6]3[CH:5]=[CH:4][CH:3]=[CH:2][C:1]=3[N:7]=2)[C:10]([F:18])=[CH:11][CH:12]=1)([O-:17])=[O:16]
Reactant: O=C(Nc1ccccc1)c1cc([N+](=O)[O-])ccc1F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Product: O=[N+]([O-])c1ccc(F)c(-c2nc3ccccc3o2)c1

Procedure:
Prepared by the method of Example 15c), from N-phenyl-2-fluoro-5-nitrobenzamide (2.89 g, 10.4 mmol) and p-toluenesulfonic acid monohydrate (3.80 g, 20.0 mmol) the subtitle compound was obtained (2.41 g, 90%). 1H NMR (DMSO) δ 8.95(m, 1H), 8.52(m, 1H), 7.90(m, 2H), 7.81(t, 1H), 7.50(m, 2H).
Reaction SMILES: FC(F)(F)C([NH:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:21])[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][N:9]2[C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1)=O>CC(=O)OCC>[NH2:5][C:6]1[N:7]=[C:8]2[CH:13]=[CH:12][C:11]([C:14](=[O:21])[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:10][N:9]2[C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1
Reactant: O=C(c1ccccc1)c1ccc2nc(NC(=O)C(F)(F)F)c(-c3cccc(Cl)c3)n2c1
Solvent: CCOC(C)=O
Product: Nc1nc2ccc(C(=O)c3ccccc3)cn2c1-c1cccc(Cl)c1

Procedure:
The 2-trifluoroacetamido-3-(3-chlorophenyl)-6-benzoyl-imidazo[1,2-a]pyridine (8.97 g, 20.2 mmol) was converted to product in a manner substantially analogous to Example 67 to yield 6.05 g. (86.1%). EA, MS(FD).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)C.[C:12]1([CH:18]([CH2:23][C:24](O)=[O:25])[CH2:19][C:20](O)=[O:21])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O>O1CCCC1>[C:12]1([CH:18]([CH2:19][CH2:20][OH:21])[CH2:23][CH2:24][OH:25])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(O)CC(CC(=O)O)c1ccccc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOCC
Product: OCCC(CCO)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 9.10 g (240 mM) of lithium aluminum hydride in tetrahydrofuran (500 ml)-diethyl ether (200 ml) was added a solution of 24.960 g (119.9 mM) of 3-phenylglutaric acid in 100 ml of tetrahydrofuran dropwise with ice-cooling and the mixture was stirred at room temperature overnight. To this reaction mixture was added water gradually dropwise under ice-cooling until a precipitate had formed. The precipitate was filtered off with the aid of celite and washed with ethyl acetate. The filtrate and washes were pooled and the solvent was distilled off under reduced pressure to provide crude 3-phenylpentane-1,5-diol. This crude product was not purified but used as it was in the next reaction. (Brown liquid, yield 19.19 g).