Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][C:4]=1[O:10][CH2:11][CH2:12][O:13][CH3:14].C([O:17][CH:18]=[C:19](C(OCC)=O)[C:20](OCC)=O)C.C1(OC2C=CC=CC=2)C=CC=CC=1>>[CH3:1][O:2][C:3]1[CH:9]=[C:8]2[C:6](=[CH:5][C:4]=1[O:10][CH2:11][CH2:12][O:13][CH3:14])[NH:7][CH:20]=[CH:19][C:18]2=[O:17]
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: COCCOc1cc(N)ccc1OC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: COCCOc1cc2[nH]ccc(=O)c2cc1OC
Temperature: 240 °C
Yield: 7.9 %

Procedure:
A solution of 4-methoxy-3-(2-methoxyethoxy)aniline (5 g, 25.3 mmol) and diethyl ethoxymethylenemalonate (6 ml, 30 mmol) was heated at 110° C. for 30 minutes. Phenyl ether (5 ml) was added and the mixture was heated at 240° C. for 6 hours. The mixture was allowed to cool and diluted with petroleum ether. The resulting solid was collected by filtration and purified by reverse phase chromatography on a Diaion (trade mark of Mitsubishi) HP20SS resin column eluting with acetonitrile/water (40/60) to give 6-methoxy-7-(2-methoxyethoxy)-1,4-dihydroquinolin-4-one (500 mg, 8%).
Reaction SMILES: [CH:1]([NH:4][CH2:5][CH:6]([CH2:13][O:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1)[N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)(C)[CH3:2].Cl>>[CH2:1]([NH:4][CH2:5][CH:6]([CH2:13][O:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1)[N:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[CH3:2]
Reactant: CC(C)NCC(COc1cccc2ccccc12)N1CCCCC1
Agent: Cl
Product: CCNCC(COc1cccc2ccccc12)N1CCCCC1

Procedure:
N-isopropyl-β-[(1-naphthyloxy)methyl]-1-piperidineethanamine mmr (CDCl3) δ 1.12 (3, 9H), 1.5 (m, 6H), 2.08 (s, 1H), 2.85 (m, 7H), 4.25 (m, 2) and 6.8 - 8.4 (m, 7H), the corresponding hydrochloric acid addition salt (hydrochloride) of the latter compound has mp 182-184° C., after recrystallization from ethyl acetate-methanol-diethyl ether,
Reaction SMILES: [F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21](I)[C:16]2=[CH:15][N:14]=1.CC1(C)C(C)(C)OB([C:31]2[CH:40]=[C:39]3[C:34]([CH2:35][CH2:36][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38]3)=[CH:33][CH:32]=2)O1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O>[F:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]2[NH:19][N:20]=[C:21]([C:31]3[CH:40]=[C:39]4[C:34]([CH2:35][CH2:36][N:37]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:38]4)=[CH:33][CH:32]=3)[C:16]2=[CH:15][N:14]=1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(B3OC(C)(C)C(C)(C)O3)cc2C1
Reactant: COc1cc(OC)c(F)c(-c2ncc3c(I)n[nH]c3n2)c1F
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Solvent: ClCCl
Product: COc1cc(OC)c(F)c(-c2ncc3c(-c4ccc5c(c4)CN(C(=O)OC(C)(C)C)CC5)n[nH]c3n2)c1F
Temperature: 115 °C
Reaction time: 3 h

Procedure:
A mixture of 6-(2,6-difluoro-3,5-dimethoxyphenyl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidine (16.7 mg, 0.0400 mmol), tert-butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (17.96 mg, 0.05000 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (2.0 mg, 0.0024 mmol) and potassium phosphate (25.5 mg, 0.120 mmol) in 1,4-dioxane (0.50 mL) and water (0.15 mL) in a reaction vial was sealed, and degassed and recharged with nitrogen for three times. The mixture was stirred at 115° C. for 3 h. After cooling, the mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=524.1.
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([C:13]=2[CH:15]=O)=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[CH:17]1([CH2:22][NH2:23])[CH2:21][CH2:20][CH2:19][CH2:18]1.[BH4-].[Na+].Cl>C(O)C>[CH:17]1([CH2:22][NH:23][CH2:15][C:13]2[C:14]3[C:5]([CH:6]=[C:7]4[C:12]=2[CH:11]=[CH:10][CH:9]=[CH:8]4)=[CH:4][CH:3]=[CH:2][CH:1]=3)[CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: O=Cc1c2ccccc2cc2ccccc12
Reactant: NCC1CCCC1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: c1ccc2c(CNCC3CCCC3)c3ccccc3cc2c1
Reaction time: 0.5 h
Yield: 96.8 %

Procedure:
A mixture of 43.5 g of 9-anthraldehyde, 20.97 g of cyclopentylmethylamine and 150 ml of ethanol is heated under reflux for 1.5 hours. The hot solution of N-cyclopentylmethyl-9-anthracenemethyleneimine so obtained is allowed to cool to 60°, and 8.2 g of sodium borohydride is added in small portions, with stirring, while the temperature is maintained at 55-60°. The mixture is then stirred for another 1.5 hours, concentrated hydrochloric acid (35 ml) is added with cooling, and stirring is continued for 0.5 hour. The mixture is then made basic and extracted with methylene chloride. Removal of the solvent from the dried extracts gives 59.1 g of N-cyclopentylmethyl-9-anthracenemethylamine as an oil; nmr spectrum: τ 1.8-3.1 (m, 9); 5.6 (s, 2), 7.5 (d, 7Hz, 2) and 7.8-9.3 (m, 10).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:35])[CH:5]([C:28]1[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[N:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:8]=1)[CH3:2].[CH3:36][Si]([N-][Si](C)(C)C)(C)C.[Na+].IC>C1COCC1>[CH2:1]([O:3][C:4](=[O:35])[C:5]([CH3:36])([C:28]1[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=1)[CH2:6][C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[N:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:8]=1)[CH3:2]
Reactant: CCOC(=O)C(Cc1cc(-c2ccc(Cl)c(Cl)c2)n(-c2ccc(OC)cc2)n1)c1cccc(C)c1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Product: CCOC(=O)C(C)(Cc1cc(-c2ccc(Cl)c(Cl)c2)n(-c2ccc(OC)cc2)n1)c1cccc(C)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 60 %

Procedure:
To a solution of 3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid ethyl ester (Method 2, product from alkylation step before hydrolysis) (50 mg, 0.10 mmol) in THF (1.0 mL) at 0° C. was added a 1.0 M solution of NaHMDS (0.15 mL, 0.15 mmol). The solution was stirred at 0° C. for 2 h, then iodomethane (41 mg, 0.29 mmol) was added neat. After stirring for 1 h the reaction was quenched with saturated ammonium chloride (50 mL), and the reaction mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (1×50 mL) and dried with Na2SO4, and the solvent was removed under reduced pressure. The crude material was purified by flash chromatography (EtOAc/hexanes) giving 31 mg (60%) of 3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-methyl-2-m-tolyl-propionic acid ethyl ester. HPLC: Rt=3.79 (Method B). MS (ES+): mass calculated for C29H28Cl2N2O3, 522.15; m/z found 523.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 7.58 (d, J=8.4 Hz, 1H), 7.42 (d, J=2.0 Hz, 1H), 7.25 (t, J=7.6 Hz, 1H), 77.17-7.14 (m, 4H), 7.08 (d, J=7.4 Hz, 1H), 7.05 (dd, J=2.0 Hz, 8.3 Hz, 1H), 6.97 (d, J=8.9 Hz, 2H), 6.22 (s, 1H), 4.10 (m, 2H), 3.77 (s, 3H), 3.40 (d, J=13.9 Hz, 1H), 3.17 (d, J=13.9 Hz, 1H), 2.13 (s, 3H), 1.49 (s, 3H), 1.12 (t, J=7.1 Hz, 3H).
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:16][C:6]2=[CH:7][C:8]3[C:9]([CH3:15])=[CH:10][CH:11]=[N:12][C:13]=3[CH:14]=[C:5]2[CH:4]=[CH:3]1.ClC1C=CC=C(C(OO)=O)C=1.[CH2:29]([N:31](CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.C(#N)C.CO>[CH3:1][C:2]1([CH3:17])[O:16][C:6]2=[CH:7][C:8]3[C:9]([CH3:15])=[CH:10][C:11]([C:29]#[N:31])=[N:12][C:13]=3[CH:14]=[C:5]2[CH:4]=[CH:3]1
Reactant: Cc1ccnc2cc3c(cc12)OC(C)(C)C=C3
Reactant: CCN(CC)CC
Agent: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: ClC(Cl)Cl
Solvent: CO
Product: Cc1cc(C#N)nc2cc3c(cc12)OC(C)(C)C=C3
Temperature: 25 °C
Reaction time: 1 h
Yield: 55 %

Procedure:
To a solution of 2,2,9-trimethyl-2H-pyrano[2,3-g]quinoline (4.36 g, 19.3 mmol) in chloroform (43.6 mL), a solution of m-chloroperbenzoic acid (7.35 g, 42.6 mmol) in chloroform (17.4 mL)-methanol (4.36 mL) was added dropwise at room temperature and the resulting mixture was stirred at room temperature for 1 hour. Upon the completion of the reaction, the reaction solution was extracted with sodium thiosulfate aqueous solution and the resulting organic phase was washed with sodium hydrogencarbonate aqueous solution and then with sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. After distilling off the solvent, acetonitrile (19.3 mL), trimethylsilylnitrile (7.27 mL, 57.9 mmol) and triethylamine (5.38 mL, 38.6 mmol) were added to the residue at room temperature, and the resulting solution was stirred at 70° C. for 3.5 hours. Upon the completion of the reaction, sodium hydrogencarbonate aqueous solution was added to the reaction solution, and it was extracted with chloroform and dried over anhydrous magnesium sulfate. After distilling off the solvent, the residue was purified by column chromatography (hexane/ethyl acetate=2/1) and the aimed product was obtained (yield: 55%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[C:3]=1[C:4]([OH:6])=O.[NH2:14][CH:15]1[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:17][CH2:16]1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)CC)C>C(OCC)(=O)C>[CH2:21]([N:18]1[CH2:19][CH2:20][CH:15]([NH:14][C:4](=[O:6])[C:3]2[C:7]([N+:11]([O-:13])=[O:12])=[CH:8][CH:9]=[CH:10][C:2]=2[Cl:1])[CH2:16][CH2:17]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: O=C(O)c1c(Cl)cccc1[N+](=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: O=C(NC1CCN(Cc2ccccc2)CC1)c1c(Cl)cccc1[N+](=O)[O-]
Temperature: 40 °C
Reaction time: 2 h
Yield: 85.1 %

Procedure:
2-Chloro-6-nitro-benzoic acid (1.2 g, 5.97 mmol), 4-amino-1-benzylpiperidine (1.1 mL, 5.97 mmol), 1-hydroxybenzotriazole (0.84 g, 1.05 equiv) and 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (1.1 g, 1.05 equiv) were combined in ethyl acetate (20 mL). To this solution was added triethylamine (2.5 mL. 3.0 equiv) and the reaction mixture stirred at 40° C. for 2 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and washed with water (2×), 5% sodium bicarbonate, brine (2×), dried over sodium sulfate, and concentrated to afford 1.9 g (85%) of the desired product.
Reaction SMILES: CC[O:3]C(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:32][C@@H:33]([OH:40])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39].F[C:42]1[C:47](F)=[C:46](CC[C@H]2CC[C@H](CCCCC)CC2)[CH:45]=[CH:44][C:43]=1[C:62]1[N:67]=[CH:66][C:65]([C:68]([O:70]C[C@H](F)CCCCCC)=O)=[CH:64][N:63]=1>C(Cl)(Cl)Cl.C1COCC1>[OH:3][C:46]1[CH:45]=[CH:44][C:43]([C:62]2[N:67]=[CH:66][C:65]([C:68]([O:40][C@@H:33]([CH3:32])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])=[O:70])=[CH:64][N:63]=2)=[CH:42][CH:47]=1
Reactant: CCCCCC[C@@H](C)O
Reactant: CCCCCC[C@@H](F)COC(=O)c1cnc(-c2ccc(CC[C@H]3CC[C@H](CCCCC)CC3)c(F)c2F)nc1
Reactant: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: CCCCCC[C@H](C)OC(=O)c1cnc(-c2ccc(O)cc2)nc1
Yield: 48 %

Procedure:
--Quantities: hydroxy acid 59 (716 mg, 3.28 mmol), DEAD (572 mg, 3.28 mmol), triphenylphosphine (861 mg, 3.28 mmol), (R)-(-)-octan-2-ol (428 mg, 3.28 mmol), THF (100 ml). The experimental procedure was as described for compound 47. Flash chromatography (10% ethyl acetate-light petroleum) gave the 1-methylheptyl ester 60 (520 mg, 48%) (from EtOH/AcOH), m.p.98.8° C., [α]D22 +44.7° (c 1.7 in CHCl3); νmax /cm-1 (KBr) 3440br, 2920, 1670, 1570, 1430, 1345, 1300, 1165 and 810; δ 0.88 (3H, t), 1.20-1.50 (11H, m), 1.70 (2H, m, CH2CHMe), 5.22 (1H, sext, OCHMe), 6.10 (1H, br s), 6.94 (2H, d, 3'- and 5'-H), 8.42 (2H, d, 2'- and 6'-H) and 9.27 (2H s, 4- and 6-H); m/z 328 (M+),314, 285, 261, 247 216 and 119.
Reaction SMILES: [K].[CH3:2][C:3]1[CH:4]=[C:5]([SH:10])[CH:6]=[C:7]([CH3:9])[CH:8]=1.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1>CN1CCCC1=O>[CH3:9][C:7]1[CH:6]=[C:5]([S:10][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)[CH:4]=[C:3]([CH3:2])[CH:8]=1
Reactant: Cc1cc(C)cc(S)c1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: [K]
Solvent: CN1CCCC1=O
Product: Cc1cc(C)cc(Sc2ccc([N+](=O)[O-])cc2)c1
Temperature: 160 °C
Reaction time: 5 h
Yield: 63.3 %

Procedure:
0.25 g (0.0014 mol) of 3,5-dimethylthiophenol potassium salt were dissolved in 5 ml of 1-methyl-2-pyrrolidone, treated with 0.19 g (0.00134 mol) of 1-fluoro-4-nitrobenzene and a spatula tip of Cu powder and stirred at 160° C. for about 5 hrs. Thereafter, the solvent was removed by distillation, the residue was partitioned in water/ethyl acetate and the organic phase was washed with sat. sodium chloride solution and dried over MgSO4. After filtration and removal of the solvent the residue was chromatographed on silica gel with ethyl acetate/hexane 1:15. There was obtained 0.22 g (62%) of 1,3-dimethyl-5-(4-nitrophenylsulphanyl)-benzene as a viscous, yellow oil. MS (EI): me/e=259 (C14H13NO2S+).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6]C)=[O:4].[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH3:24])[CH:22]=3)[N:17]([CH:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[CH:16]=2)=[CH:11][CH:10]=1.C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH3:24])[CH:22]=3)[N:17]([CH:25]3[CH2:30][CH2:29][N:28]([CH2:2][C:3]([O:5][CH3:6])=[O:4])[CH2:27][CH2:26]3)[CH:16]=2)=[CH:11][CH:10]=1
Reactant: CCOC(=O)CBr
Reactant: Cc1ccc2c(c1)c(-c1ccc(F)cc1)cn2C1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)CN1CCC(n2cc(-c3ccc(F)cc3)c3cc(C)ccc32)CC1

Procedure:
A solution of ethyl bromoacetate in acetone was added during 15 min to a mixture of 3-(4-fluorophenyl)-5-methyl-l-(4-piperidyl)-1H-indole 3d (5.0 g), K2CO3 (2.5 g) and acetone (100 ml) at room temperature. After another 2 h the solvents were evaporated, water was added and the mixture was extracted with ethyl acetate (2×100 ml). The combined organic phases were washed with brine and dried (Na2SO4). Evaporation of the solvent afforded the crude methyl 4-[3-(4-fluorophenyl)-5-methyl-1H-indol-1-yl]1-piperidinacetate (6.0 g), which was used without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[C:18]([CH3:25])[CH:17]=2)=[N:4][N:3]=1.[BH4-].[Na+]>ClCCl.CO.C(O)(=O)C>[CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[C:18]([CH3:25])[CH:17]=2)=[N:4][NH:3]1
Reactant: CC1=NN=C(c2ccc([N+](=O)[O-])c(C)c2)c2cc3c(cc2C1)OCO3
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Solvent: CC(=O)O
Product: Cc1cc(C2=NNC(C)Cc3cc4c(cc32)OCO4)ccc1[N+](=O)[O-]
Yield: 35.4 %

Procedure:
1.69 g (10.0 millimoles) of 8-methyl-5-(3-methyl-4-nitro-phenyl)-9H-1,3-dioxolo[4,5-h][2,3]benzodiazepine are dissolved in a mixture of 75 ml of dichloro methane, 5 ml of methanol and 3 ml of glacial acetic acid. To the reaction mixture 0.38 g (10.0 millimoles) of sodium borohydride are added under cooling with ice-cold water in small portions. The reaction mixture is stirred at this temperature for an hour, then washed twice with 20 ml of water and 20 ml of saturated sodium chloride solution each, washed over magnesium sulfate and evaporated in vacuo. The crude product obtained is recrystallized from 50 ml of acetonitrile each. Thus 1.20 g of the desired compound are obtained, yield 71%, mp.: 124–127° C.
Reaction SMILES: CO[N:3]=[C:4]1[C@@H:9]([CH2:10][O:11][Si:12]([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][C@H:7]2[CH2:29][C@@H:5]1[C:6]2([CH3:31])[CH3:30].B.C1COCC1.[OH-].[Na+]>C1COCC1>[Si:12]([O:11][CH2:10][C@H:9]1[CH2:8][C@H:7]2[CH2:29][C@H:5]([C:6]2([CH3:31])[CH3:30])[CH:4]1[NH2:3])([C:25]([CH3:28])([CH3:26])[CH3:27])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CON=C1[C@@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C[C@H]2C[C@@H]1C2(C)C
Agent: B
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CC1(C)[C@H]2C[C@H](CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)C(N)[C@@H]1C2
Temperature: 75 °C

Procedure:
To a solution of (1R,3S,5R)-3-(((tert-butyldiphenylsilyl)oxy)methyl)-6,6-dimethyl-bicyclo[3.1.1]heptan-2-one O-methyl oxime, 77d, (0.20 g, 0.46 mmol) in THF (3 mL) was added borane-THF (1.38 mL of 1 M solution, 1.38 mmol). The reaction was heated to 75° C. for 18 hours. The mixture was diluted into 1N NaOH (50 mL) and extracted twice with EtOAc. The combined organic phases were dried (MgSO4), filtered and concentrated in vacuo to afford 178 mg of a colorless oil that was used without further purification: LCMS RT=2.53 (M+H) 408.54.
Reaction SMILES: C([O:8][C:9]([C:11]1[CH:12]([C:30]2[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=2)[C:13]([C:23]([O:25][CH2:26][CH2:27][C:28]#[N:29])=[O:24])=[C:14]([CH2:20][CH2:21][CH3:22])[NH:15][C:16]=1[CH2:17][CH2:18][CH3:19])=[O:10])C1C=CC=CC=1.C(O)=O.CO>C(Cl)(Cl)Cl.[Pd]>[C:28]([CH2:27][CH2:26][O:25][C:23]([C:13]1[CH:12]([C:30]2[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=2)[C:11]([C:9]([OH:10])=[O:8])=[C:16]([CH2:17][CH2:18][CH3:19])[NH:15][C:14]=1[CH2:20][CH2:21][CH3:22])=[O:24])#[N:29]
Reactant: CCCC1=C(C(=O)OCCC#N)C(c2ccc([N+](=O)[O-])cc2)C(C(=O)OCc2ccccc2)=C(CCC)N1
Agent: [Pd]
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: O=CO
Product: CCCC1=C(C(=O)O)C(c2ccc([N+](=O)[O-])cc2)C(C(=O)OCCC#N)=C(CCC)N1
Reaction time: 1 h

Procedure:
A solution of 5-benzyloxycarbonyl-3-(2-cyanoethoxy) carbonyl-1,4-dihydro-4-(4-nitrophenyl)-2,6-dipropylpyridine (10.6 g, 20.4 mmol) in 200 ml of 4.4%(w/w) formic acid/MeOH mixture was stirred with Pd/C (10%, 3.50 g) at room temperature. After 1 hr, the reaction was quenched by addition of 50 ml of CHCl3. The mixture was filtered and concentrated to give a yellow powder, which was dissolved in CHCl3 (250 ml), washed with 0.5N aqueous HCl (100 ml) and brine (100 ml), then dried over Na2SO4. After filtration and evaporation of solvent, 3-(2-cyanoethoxy) carbonyl-1,4-dihydro-4-(4-nitrophenyl)-2,6-dipropylpyridine-5-carboxylic acid was obtained as a yellow powder (8.04 g, 92%).
Reaction SMILES: Cl[CH:2]([C:11]1[N:15]([CH3:16])[CH:14]=[N:13][CH:12]=1)[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[NH4+:17].[OH-]>C1COCC1.ClCCl>[NH2:17][CH:2]([C:11]1[N:15]([CH3:16])[CH:14]=[N:13][CH:12]=1)[C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1
Reactant: [NH4+]
Reactant: Cn1cncc1C(Cl)c1ccc(C#N)cc1
Agent: [OH-]
Solvent: ClCCl
Solvent: C1CCOC1
Product: Cn1cncc1C(N)c1ccc(C#N)cc1
Reaction time: 2 h
Yield: 77 %

Procedure:
A suspension of Example 41E (200 mg, 0.746 mmol) in THF (5 mL) at room temperature was treated dropwise with concentrated NH4OH (2.0 mL), stirred for 2 hours, diluted with dichloromethane, washed with water, dried (MgSO4), filtered, and concentrated to provide 123 mg (77%) of the desired product. MS (ESI) m/z 213 (M+H)+; 1H NMR (CDCl3) δ 7.65 (m, 2H), 7.48 (m, 2H), 7.39 (s, 1H), 6.84 (s, 1H), 5.26 (s, 1H), 3.49 (s, 3H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1)=O)([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+].C([BH3-])#[N:25].[Na+]>CO>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][CH:9]([NH2:25])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCC(=O)c1cccc(F)c1
Reactant: [BH3-]C#N
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)NCC(N)c1cccc(F)c1
Yield: 91 %

Procedure:
To a flask were added tert-butyl[2-(3-fluorophenyl)-2-oxoethyl]carbamate (0.32 g, 1.3 mmol) and ammonium acetate (2.02 g, 26.2 mmol) and methanol (10 mL) and sodium cyanoborohydride (0.22 g, 3.5 mmol). The mixture was refluxed for 2 h. The solvent was removed under vacuum. To the residue was added EtOAc and 50 mL of 1M NaOH. The aqueous phase was extracted again with fresh EtOAc. The combined organic extracts were dried over sodium sulfate, filtered and dried under vacuum to give 0.301 g (94% yield) of the final product as oil. LC-MS found: 155.1 (M−Boc)+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].S([O:12][CH3:13])(OC)(=O)=O.[CH2:14]([O:21][C:22]1[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24](O)[CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(#N)C>[CH2:14]([O:21][C:22]1[C:31]([CH:32]([CH3:34])[CH3:33])=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([O:12][CH3:13])[CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1cc(C(C)C)c(OCc2ccccc2)cc1O
Reactant: COS(=O)(=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1cc(C(C)C)c(OCc2ccccc2)cc1OC
Temperature: 25 °C
Yield: 94.4 %

Procedure:
Anhydrous potassium carbonate (450 mg, 3.26 mmol) and dimethyl sulphate (0.25 ml, 2.64 mmol) were added to a suspension of methyl 4-benzyloxy-2-hydroxy-5-isopropylbenzoate (650 mg, 2.17 mmol) in acetonitrile (20 ml) and the mixture was stirred and held at reflux for 16 hours. Upon cooling to room temperature the solvent was removed in vacuo and the residue acidified by the addition of 2M hydrochloric acid (20 ml). The organic material was extracted with ethyl acetate (2×30 ml) and the combined organic extracts were evaporated in vacuo to afford methyl 4-benzyloxy-5-isopropyl-2-methoxybenzoate (644 mg, 95%) as a pale yellow solid. 1H NMR (DMSO-d6) 7.56 (1H, s), 7.50 (2H, d), 7.43 (2H, t), 7.37 (1H, t), 6.80 (1H, s), 5.26 (2H, s), 3.83 (3H, s), 3.75 (3H, s), 3.19 (1H, m), 1.17 (6H, d). MS: [M+H]+ 315.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:19])=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15])=[CH:9][CH:8]=[C:7]([Br:18])[CH:6]=2.[N:20]#[C:21]Br>C(O)C>[BrH:18].[NH2:20][C:21]1[N:12]([CH2:13][C:14]([CH3:17])([OH:16])[CH3:15])[C:11]2[C:10]3[CH:9]=[CH:8][C:7]([Br:18])=[CH:6][C:5]=3[N:4]=[C:3]([Cl:19])[C:2]=2[N:1]=1
Reactant: CC(C)(O)CNc1c(N)c(Cl)nc2cc(Br)ccc12
Reactant: N#CBr
Solvent: CCO
Product: Br
Product: CC(C)(O)Cn1c(N)nc2c(Cl)nc3cc(Br)ccc3c21
Temperature: 80 °C
Yield: 136.7 %

Procedure:
A suspension of 1-[(3-amino-7-bromo-2-chloroquinolin-4-yl)amino]-2-methylpropan-2-ol (1.5 g, 4.35 mmol) in ethanol (25 mL) was heated to 80° C. Cyanogen bromide (0.50 g, 4.8 mmol) was added to the resulting solution, and the reaction was heated at 80° C. overnight and allowed to cool. A precipitate was present and was isolated by filtration, washed with diethyl ether, and dried under vacuum for one hour to provide 1.34 g of 1-(2-amino-7-bromo-4-chloro-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol hydrobromide as a pinkish-white solid, mp >260° C.
Reaction SMILES: [OH:1][CH:2]([CH2:7][N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[CH2:3][N:4]=[N+]=[N-].[H][H]>[OH-].[OH-].[Pd+2]>[OH:1][CH:2]([CH2:7][N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[CH2:3][NH2:4]
Reactant: [H][H]
Reactant: [N-]=[N+]=NCC(O)CN1CCOCC1
Agent: [Pd+2]
Agent: [OH-]
Product: NCC(O)CN1CCOCC1
Yield: 84.4 %

Procedure:
A methanolic solution of 81 (11 g, 59.14 mmol), was shaken with 20% palladium hydroxide on Carbon (2 g) under 40 psi pressure of hydrogen for 20 hours. The mixture was filtered through celite and the filter cake was thoroughly washed with methanol and dichloromethane. The solvent was removed under vacuum to give 82 (8 g, 93%) as a light yellow oil; 1H NMR (300 MHz, CDCl3) δ3.8-3.6 (m, 4H), 3.42 (m, 1H), 2.8 (br d, 1H), 2.7-2.55 (m, 2H), 2.55-2.2 (m, 6H).