Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SH2:1].[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6]([C:10]#[N:11])=[CH:5][N:4]=1.C(N(CC)CC)C.N1C=CC=CC=1>CS(C)=O.O>[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6]([C:10](=[S:1])[NH2:11])=[CH:5][N:4]=1
Reactant: N#Cc1cnc(N)nc1N
Reactant: S
Solvent: c1ccncc1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: NC(=S)c1cnc(N)nc1N

Procedure:
Hydrogen sulfide is passed into a mixture of 2,4-diamino-5-pyrimidine carbonitrile (10.000 g., 0.0740 mole), triethylamine (10.3 ml., 0.0740 mole) and pyridine (6.0 ml., 0.074 mole) in dimethyl sulfoxide (100 ml.) for one-half hour. After storage at room temperature overnight, the brown solution is poured into water (500 ml.) with stirring. The product separates as a yellow crystalline solid which is collected by filtration, washed with water, dried at 56° C./0.1 mm. The yield of crude product melting at greater than 325° C. (uncorr.) is 12.020 g. (96.0%). Recrystallization of this material from 2-methoxyethanol affords the title compound as tan crystals melting above 350° C. (uncorr.) after drying at 110° C. at 0.1 mm.
Reaction SMILES: I[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]>[Cu]>[N+:9]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=1[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10])([O-:11])=[O:10]
Reactant: Cc1cccc([N+](=O)[O-])c1I
Agent: [Cu]
Product: Cc1cccc([N+](=O)[O-])c1-c1c(C)cccc1[N+](=O)[O-]

Procedure:
The 2,2'-bis(diarylphosphino)-6,6'-dimethylbiphenyl, the other starting material, can be synthesized according to the process reported in Miyashita et al., The Chemical Society of Japan, Collected Drafts II for Lectures in the 52th Spring Annual Meeting, IT06, p. 1267 (1986). More specifically, o-toluidine is reacted with nitric acid to form 2-amino-3-methylnitrobezene, which is then converted to 2-iodo-3-methylnitrobenzene making use of the process described in P.B. Carlin et al., J. Am. Chem. Soc., Vol. 78, p. 1997 (1956). A copper powder is reacted on the resulting product to obtain 2,2'-dinitro-6,6'-dimethylbiphenyl, which is then subjected to hyrogenation using a Raney nickel as a catalyst to obtain 2,2'-diamino-6,6'-dimethylbiphenyl. The product is treated with a 47% hydrobromic acid aqueous solution to obtain 2,2'-dibromo-6,6'-dimethylbiphenyl. A Grignard reagent is prepared from the product according to a process generally employed therefor, for example, by using magnesium. The resulting Grignard reagent is condensed with a diarylphosphinyl chloride selected from diphenylphosphinyl chloride, di-p-tolylphosphinyl chloride, and di-p-anisylphosphinyl chloride to obtain a (±)-2,2 '-bis(diarylphosphino)-6,6'-dimethylbiphenyl. The product is resolved by using benzoyl tartrate and then reduced with trichlorosilane to obtain an optically active 2,2'-bis(diarylphosphino)-6,6'-dimethylbiphenyl. Starting with the thus prepared optically active 2,2'-bis(diarylphosphino)-6,6'-dimethylbiphenyl, there can be obtained the ruthenium-phosphine complex of the present invention having the corresponding optical activity.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[N:10]=[C:11]3[C:17]4[CH:18]=[CH:19][C:20]([CH2:22][C:23](O)=[O:24])=[CH:21][C:16]=4[O:15][CH2:14][CH2:13][N:12]3[CH:26]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[NH2:27][OH:28]>>[OH:28][NH:27][C:23](=[O:24])[CH2:22][C:20]1[CH:19]=[CH:18][C:17]2[C:11]3[N:12]([CH:26]=[C:9]([C:8]4[N:4]([CH:1]([CH3:2])[CH3:3])[N:5]=[CH:6][N:7]=4)[N:10]=3)[CH2:13][CH2:14][O:15][C:16]=2[CH:21]=1
Reactant: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(CC(=O)O)cc1OCC2
Reactant: NO
Product: CC(C)n1ncnc1-c1cn2c(n1)-c1ccc(CC(=O)NO)cc1OCC2

Procedure:
Following the procedures of Example 316, 2-(2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)acetic acid and hydroxylamine were reacted to give 352. M/z 369.1, calc. 368.16. 1H NMR (400 MHz, DMSO) δ 10.69 (s, 1H), 8.88 (s, 1H), 8.32 (d, J=8.2, 1H), 7.92 (d, J=2.9, 2H), 7.04 (d, J=8.2, 1H), 6.97 (s, 1H), 5.95-5.81 (m, 1H), 4.50 (d, J=5.7, 4H), 3.29 (s, 2H), 1.48 (d, J=6.6, 6H)
Reaction SMILES: C([O:8][C:9]1[C:10](=[O:32])[N:11]([CH2:15][C:16](=[O:31])[N:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[H][H]>CCO.[Pd].[Fe+3]>[OH:8][C:9]1[C:10](=[O:32])[N:11]([CH2:15][C:16](=[O:31])[N:17]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][CH:14]=1
Reactant: [H][H]
Reactant: O=C(Cn1cccc(OCc2ccccc2)c1=O)N(Cc1ccccc1)c1ccccc1
Agent: [Fe+3]
Agent: [Pd]
Solvent: CCO
Product: O=C(Cn1cccc(O)c1=O)N(Cc1ccccc1)c1ccccc1
Yield: 22 %

Procedure:
18 (280 mg, 0.7 mmol) was suspended in 150 mL of EtOH. 10% (w/w, 38 mg) of 10% Pd/C catalyst was added to the hydrogenation flask (500 mL Pyrex® Parr reaction bottle tested to 120 psi, max. working pressure of 60 psi). The Parr hydrogenation system located in the VanNieuwenhze lab was used for the deprotection reactions. The hydrogen pressure was set to 35 psi with agitation, and the process went on for 19 h. A white precipitate was present even after the reaction was stopped, but this white product reacted with iron(III) to give a pink product instead of no reaction as with the protected starting material. The catalyst was removed by vacuum filtration and separated from the product by dissolving the white precipitate in 100 mL hot CH2Cl2. An additional batch of product was isolated by cooling the EtOH filtrate to 0° C. for 2 h. The clear solution was concentrated by rotary evaporation to yield a white solid. The solid was washed with MeOH to remove residual DCU. Yield: 22%. 1H NMR (d6-DMSO, 400 MHz, 25° C.): δ 4.34 (d, J=6.0 Hz, 2H, —CH2—), 4.63 (s, 2H, —CH2—), 6.08 (t, J=7.2 Hz, 1H, Ar—H), 6.69 (d, J=7.2 Hz, 1H, Ar—H), 7.10 (d, J=6.4 Hz, 1H, Ar—H), 7.44 (m, 5H, Bz-H), 7.64 (m, 4H, Phenyl-H), 8.70 (t, J=5.6 Hz, 1H, —NH—), 9.02 (s, 1H, —OH). APCI-MS: m/z 334.9 [M+H]+. Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.49; H, 5.78; N, 8.52.
Reaction SMILES: [CH2:1]([N:8]([S:16]([CH2:19][CH2:20][CH2:21]Cl)(=[O:18])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][NH:24][CH2:25][CH2:26][NH:27][CH3:28].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH2:1]([N:8]([S:16]([CH2:19][CH2:20][CH2:21][N:24]([CH3:23])[CH2:25][CH2:26][NH:27][CH3:28])(=[O:18])=[O:17])[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CNCCNC
Reactant: CC(C)(C)OC(=O)N(Cc1ccccc1)S(=O)(=O)CCCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CNCCN(C)CCCS(=O)(=O)N(Cc1ccccc1)C(=O)OC(C)(C)C
Temperature: 65 °C
Reaction time: 8 h

Procedure:
Tert-butyl benzyl[(3-chloropropyl)sulfonyl]carbamate was dissolved in MeCN (0.2M) and N,N′-dimethylethane-1,2-diamine (5 eq.) was added followed by K2CO3 (5 eq.). The mixture was stirred at 65° C. overnight. The solvent was removed under reduced pressure and the residual material was dissolved in EtOAc and washed with water. After drying over Na2SO4, all volatiles were evaporated in vacuo and the residual material used in the next step without purification. (ES+) m/z 400 (M+H)+.
Reaction SMILES: Cl.[CH2:2]([N:9]1[CH2:15][CH2:14][C:13](Cl)=[C:12]([CH:17]=O)[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]([NH2:28])[NH2:27])=[CH:21][CH:20]=1.C(O)(O)=O.C([O-])C.[Na+]>C(O)C>[CH2:2]([N:9]1[CH2:10][CH2:11][C:12]2[CH:17]=[N:27][C:26]([NH:25][C:22]3[CH:23]=[CH:24][CH:19]=[CH:20][CH:21]=3)=[N:28][C:13]=2[CH2:14][CH2:15]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: NC(N)=Nc1ccccc1
Reactant: O=CC1=C(Cl)CCN(Cc2ccccc2)CC1
Agent: CC[O-]
Agent: Cl
Agent: O=C(O)O
Solvent: CCO
Product: c1ccc(CN2CCc3cnc(Nc4ccccc4)nc3CC2)cc1
Temperature: 70 °C
Reaction time: 4 h
Yield: 26 %

Procedure:
1 g 1-benzyl-5-chloro-2,3,6,7-tetrahydro-1H-azepine-4-carbaldehyde hydrochloride was added to 1 g phenylguanidine carbonate salt and 1 g sodium ethanolate in 25 mL ethanol. The reaction was stirred 4 h at 70° C. The mixture was filtered over silica gel and the solvent was removed. The residue was purified by chromatography on silica gel (dichlormethane/MeOH/ammonia: 19/1/0.1) to yield 300 mg of the desired product.
Reaction SMILES: C[O:2][C:3](=[O:30])[C@@H:4]([O:27][CH2:28][CH3:29])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[F:26].[Li+].[OH-]>>[CH2:28]([O:27][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[F:26])[C:3]([OH:30])=[O:2])[CH3:29]
Reactant: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1F)C(=O)OC
Agent: [Li+]
Agent: [OH-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccccc3)oc2C)cc1F)C(=O)O

Procedure:
In analogy to the procedure described in example 1 g], (S)-2-ethoxy-3-[2-fluoro-4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid methyl ester was treated with LiOH to obtain (S)-2-ethoxy-3-[2-fluoro-4-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-phenyl]-propionic acid as colorless solid.
Reaction SMILES: C(OC(=O)N[C@@H](CC1C=CC=CC=1)[C@@H](O)C[C@H](C(=O)NCCC(C)(C)C)C)(C)(C)C.[C:31]([CH:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1)([CH3:34])([CH3:33])[CH3:32].[F:42][C:43]1[C:66]([N:67]2[CH2:71][CH2:70][CH2:69][C:68]2=[O:72])=[CH:65][C:64]([N:73]2[CH2:77][CH2:76][CH2:75][C:74]2=[O:78])=[CH:63][C:44]=1[C:45]([NH:47][C@H:48]([C@@H:56]1[CH2:60][C@@H:59]([CH3:61])[C:58](=[O:62])[O:57]1)[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:46]>>[CH2:49]([C@H:48]([NH:47][C:45](=[O:46])[C:44]1[CH:63]=[C:64]([N:73]2[CH2:77][CH2:76][CH2:75][C:74]2=[O:78])[CH:65]=[C:66]([N:67]2[CH2:71][CH2:70][CH2:69][C:68]2=[O:72])[C:43]=1[F:42])[C@@H:56]([OH:57])[CH2:60][C@H:59]([C:58](=[O:62])[NH:41][CH:38]1[CH2:37][CH2:36][CH:35]([C:31]([CH3:34])([CH3:32])[CH3:33])[CH2:40][CH2:39]1)[CH3:61])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1
Reactant: CC(C)(C)C1CCC(N)CC1
Reactant: C[C@@H]1C[C@@H]([C@H](Cc2ccccc2)NC(=O)c2cc(N3CCCC3=O)cc(N3CCCC3=O)c2F)OC1=O
Agent: C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(=O)NCCC(C)(C)C
Product: C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)c1cc(N2CCCC2=O)cc(N2CCCC2=O)c1F)C(=O)NC1CCC(C(C)(C)C)CC1

Procedure:
Prepared in an analogous manner to D1 from 4-tert-butylcyclohexylamine and 2-fluoro-N-[(S)-1-((2S,4R)-4-methyl-5-oxotetrahydrofuran-2-yl)-2-phenylethyl]-3,5-bis-(2-oxopyrrolidin-1-yl)benzamide (D50).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[S:11][C:10]=1C(O)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Cu].N1C2C(=CC=CC=2)C=CC=1>[CH2:1]([O:8][C:9]1[CH:13]=[C:12]([C:14]([F:17])([F:15])[F:16])[S:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1sc(C(F)(F)F)cc1OCc1ccccc1
Agent: [Cu]
Solvent: c1ccc2ncccc2c1
Product: FC(F)(F)c1cc(OCc2ccccc2)cs1
Temperature: 150 °C
Yield: 70.5 %

Procedure:
A mixture of 5F (14.5 g) and quinoline (50 ml) was treated with copper powder (4.57 g) and heated to 150° C. The reaction mixture is heated for 25 minutes at 150° C. and cooled to room temperature. The mixture was filtered and washed with water. Aqueous quinoline was acidified with 6N HCl (pH=2) and extracted with diethyl ether twice. The combined organic phases were washed with water and dried. The mixture was concentrated and the residue was chromatographed to yield a yellow liquid (8.74 g, 71%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]([CH:13]2[CH2:22][CH2:21][C:16]3[N:17]=[C:18]([NH2:20])[S:19][C:15]=3[CH2:14]2)[CH2:9][CH2:8]1.C(N(CC)CC)C.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][N:10]([CH:13]2[CH2:22][CH2:21][C:16]3[N:17]=[C:18]([NH:20][C:30](=[O:37])[C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[S:19][C:15]=3[CH2:14]2)[CH2:9][CH2:8]1
Reactant: Nc1nc2c(s1)CC(N1CCN(c3ccccn3)CC1)CC2
Reactant: O=C(Cl)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: O=C(Nc1nc2c(s1)CC(N1CCN(c3ccccn3)CC1)CC2)c1ccccc1

Procedure:
A solution of (±)-4,5,6,7-tetrahydro-6-[4-(2-pyridinyl)-1-piperazinyl]-2-benzothiazolamine (10.0 g) (Example 1) in 200 ml of chloroform is treated with triethylamine (6.06 g) and benzoyl chloride (4.21 g). The resulting red solution is refluxed for two hours under nitrogen. Saturated sodium bicarbonate solution is added. The organic layer is dried (magnesium sulfate) and evaporated. The residue is purified by MPLC (silica; 1.5% methanol, 98.5% dichloromethane). The title compound is obtained as a yellow solid; mp 230°-232° C.
Reaction SMILES: CN([CH2:4][C:5]1C=C(O)C=C[CH:10]=1)C.[CH3:12][N:13]([CH2:15][C:16]1[CH:17]=[C:18]([CH:25]=[CH:26][CH:27]=1)[O:19][CH2:20][CH2:21][CH2:22][CH:23]=[O:24])[CH3:14]>>[N:13]1([CH2:15][C:16]2[CH:17]=[C:18]([CH:25]=[CH:26][CH:27]=2)[O:19][CH2:20][CH2:21][CH2:22][CH:23]=[O:24])[CH2:14][CH2:10][CH2:5][CH2:4][CH2:12]1
Reactant: CN(C)Cc1cccc(OCCCC=O)c1
Reactant: CN(C)Cc1cccc(O)c1
Product: O=CCCCOc1cccc(CN2CCCCC2)c1

Procedure:
Similarly prepared from 3-[(dimethylamino)methyl]phenol (12.08 g) was 4-[3-[(dimethylamino)methyl]phenoxy]butanal (1.05 g) as a colourless oil b.p. 150°, 0.06 mm; tlc System A, Rf 0.59.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][O:8][C:9]([C:11]1[N:12]([CH:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][S:18][CH2:17]2)[CH:13]=[N:14][CH:15]=1)=O.C1C2C(=CC=CC=2)C(N2C(CO)=CN=C2)CS1.CC(C)([O-])C.[K+].IC>C1COCC1>[CH2:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:16]([N:12]2[C:11]([CH2:9][O:8][CH3:7])=[CH:15][N:14]=[CH:13]2)[CH2:17][S:18]1
Reactant: COC(=O)c1cncn1C1CSCc2ccccc21
Agent: CC(C)(C)[O-]
Agent: OCc1cncn1C1CSCc2ccccc21
Agent: [Al+3]
Solvent: CI
Solvent: C1CCOC1
Product: COCc1cncn1C1CSCc2ccccc21
Temperature: 48 °C
Reaction time: 4 h

Procedure:
To a solution of LiAlH4 (171 mg, 4.48 mmol) in THF (100 mL) at 0° C. is added a solution of 3-isothiochroman-4-yl-3H-imidazole-4-carboxylic acid methyl ester [which can be prepared from isothiochroman-4-ol (CAS#109819-33-2) as described in Example 2; MS: (ESI) m/z 275.2 (M+H)+] (1.23 g, 4.48 mmol) in THF (50 mL). The reaction is permitted to stir for 4 hours, at which time it is quenched by the slow addition of water. The reaction mixture is then filtered, diluted with ethyl acetate and washed with saturated aqueous NaHCO3. The organic layer is dried with Na2SO4, filtered, and concentrated. A portion of the resulting residue containing (3-isothiochroman-4-yl-3H-imidazol-4-yl)-methanol (240 mg, ca. 0.5 mmol) is then dissolved in THF (25 mL) and cooled to 48° C. The reaction mixture is then charged with a 1 M THF solution of potassium t-butoxide (0.75 mL, 0.75 mmol). The reaction is permitted to stir for 30 minutes and then charged with iodomethane (0.2 mL, 0.61 mmol). After 3.5 hours the reaction is quenched with saturated aqueous NaHCO3 and further diluted with ethyl acetate. The organic layer is washed with saturated aqueous NaHCO3, and then dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:19) to provide 1-isothiochroman-4-yl-5-methoxymethyl-1H-imidazole; MS: (ESI) m/z 261.1 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 3.07-3.30 (m, 2 H), 3.33 (s, 3 H), 3.88 (br. s., 2 H), 4.35-4.57 (m, 2 H), 5.64 (t, J=5.2 Hz, 1 H), 6.93 (d, J=7.1 Hz, 1 H), 7.07 (s, 1 H), 7.15-7.28 (m, 3 H), 7.39 (s, 1 H). The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 1-isothiochroman-4-yl-5-methoxymethyl-1H-imidazole.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][N:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1.Cl.[NH2:19][OH:20]>>[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][N:11]1[CH2:16][CH2:15][C:14](=[N:19][OH:20])[CH2:13][CH2:12]1
Reactant: NO
Reactant: O=C1CCN(Cc2nc3ccccc3[nH]2)CC1
Agent: Cl
Product: ON=C1CCN(Cc2nc3ccccc3[nH]2)CC1

Procedure:
1-(2-Benzimidazolyl)methyl-4-piperidone oxime is prepared from 1-(2-benzimidazolyl)methyl-4-piperidone and hydroxylamine hydrochloride essentially as described above in Example 38, Scheme C, step b.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([CH:11]=O)[C:5]=2[O:4][CH2:3][CH2:2]1.[N+:13]([CH3:16])([O-:15])=[O:14]>>[N+:13]([CH:16]=[CH:11][C:10]1[C:5]2[O:4][CH2:3][CH2:2][O:1][C:6]=2[CH:7]=[CH:8][CH:9]=1)([O-:15])=[O:14]
Reactant: O=Cc1cccc2c1OCCO2
Reactant: C[N+](=O)[O-]
Product: O=[N+]([O-])C=Cc1cccc2c1OCCO2

Procedure:
In close analogy to the procedure described above, 2,3-Dihydro-benzo[1,4]dioxine-5-carbaldehyde is reacted with nitromethane to provide the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[O:5][C:6]1[N:11]=[CH:10][C:9]([CH2:12][CH2:13][OH:14])=[CH:8][CH:7]=1.Cl[C:20]1[CH:30]=[C:24]2[N:25]([CH3:29])[CH2:26][CH2:27][CH2:28][N:23]2[C:22](=[O:31])[N:21]=1>>[F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[F:18])[O:5][C:6]1[N:11]=[CH:10][C:9]([CH2:12][CH2:13][O:14][C:20]2[CH:30]=[C:24]3[N:25]([CH3:29])[CH2:26][CH2:27][CH2:28][N:23]3[C:22](=[O:31])[N:21]=2)=[CH:8][CH:7]=1
Reactant: OCCc1ccc(Oc2ccc(F)c(F)c2)nc1
Reactant: CN1CCCn2c1cc(Cl)nc2=O
Product: CN1CCCn2c1cc(OCCc1ccc(Oc3ccc(F)c(F)c3)nc1)nc2=O

Procedure:
The title compound or its salt was prepared by a procedure similar to that described for E2 starting from 2-(6-(3,4-difluorophenoxy)pyridin-3-yl)ethanol and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one.
Reaction SMILES: [C:1]1([C@H:11]([NH2:13])[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:28]1([C@H:34]2[CH2:39][CH2:38][N:37]([C:40](=[O:45])[C:41]([F:44])([F:43])[F:42])[CH2:36][C@@H:35]2[CH:46]=O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])O.[Na+]>ClCCCl.C(O)(=O)C>[C:1]1([C@H:11]([NH:13][CH2:46][CH:35]2[CH:34]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:39][CH2:38][N:37]([C:40](=[O:45])[C:41]([F:44])([F:42])[F:43])[CH2:36]2)[CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: C[C@@H](N)c1cccc2ccccc12
Reactant: O=C[C@H]1CN(C(=O)C(F)(F)F)CC[C@@H]1c1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: C[C@@H](NCC1CN(C(=O)C(F)(F)F)CCC1c1ccccc1)c1cccc2ccccc12
Reaction time: 8 h
Yield: 82.4 %

Procedure:
To a mixture of 868 mg of (1R)-1-(1-naphthyl)ethaneamine, 0.073 mL of acetic acid, 1.29 g of sodium triacetoxyborohydride, and 75 mL of 1,2-dichloroethane was added dropwise a solution of 1.446 g of a crude rel-(3R,4S)-4-phenyl-1-(trifluoroacetyl)piperidine-3-carbaldehyde in 25 mL of 1,2-dichloroethane at room temperature, followed by stirring overnight. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, followed by vigorously stirring for 10 minutes, and then extracting with chloroform, and the organic layer was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (chloroform-methanol) to obtain 1.84 g of (1R)-1-(1-naphthyl)-N-{[4-phenyl-1-(trifluoroacetyl)piperidin-3-yl]methyl}ethaneamine as a colorless foamy substance.
Reaction SMILES: [C-:1]1([CH:6]=O)[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.[Fe+2:13].[N+:14](CC)([O-:16])=[O:15]>C(O)(=O)C>[C-:1]1([C:6]([N+:14]([O-:16])=[O:15])=[CH:12][CH3:8])[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.[Fe+2:13]
Reactant: O=C[c-]1cccc1
Reactant: CC[N+](=O)[O-]
Agent: [Fe+2]
Agent: c1cc[cH-]c1
Solvent: CC(=O)O
Product: CC=C([c-]1cccc1)[N+](=O)[O-]
Temperature: 100 °C

Procedure:
Ferrocenyl-nitropropene is prepared by reacting 2.14 g ferrocenecarboxaldehyde with 2.25 g nitroethane 1.40 g ammoniumacetate and 10 ml of glacial acetic acid during 24 hours at room temperature in the dark. After heating the reaction mixture 2 hours at 100° C. and dilution with 100 ml of ice-water the formed ferrocenyl-nitropropene is extracted with diethylether. The organic solution is washed successively with Na2S2O4 -containing water, with diluted ammonia and finally with water until neutral. After drying and evaporating the diethylether, the residue obtained is recrystalized from methanol. The desired ferrocenyl-nitropropene is obtained in a yield of 80%; m.p. 48° C.; TLC: Rf (diethylamine/diethylether 5/95) 0.86.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[O:11]=[C:12](C(OCC)=O)[C:13]([O:15]CC)=[O:14].Cl[Sn](Cl)(Cl)Cl.[OH-].[K+]>O.C(Cl)Cl>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:12]([OH:11])[C:13]([OH:15])=[O:14])=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)Cc1ccccc1
Reactant: CCOC(=O)C(=O)C(=O)OCC
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: [K+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CC(C)Cc1ccc(C(O)C(=O)O)cc1
Temperature: 0 °C
Yield: 73.8 %

Procedure:
To a dry 3-necked round-bottom flask under argon atmosphere equipped with a dropping funnel, septum and magnetic stir bar was added 12.6 mL (80 mmol) of isobutylbenzene, 12.3 mL (80 mmol) of diethyl ketomalonate (DEOM) and 40 mL of CH2Cl2. The flask was cooled with stirring to 0° C. followed by the dropwise addition of 11.7 mL (100 mmol) of SnCl4. The yellow reaction mixture was allowed to warm slowly to room temperature and after 3 hours the reaction was quenched by pouring the suspension into a mixture of 50 g of ice and 50 mL of 5% aqueous HCl and extracted with ether (3×100 mL). The ether layers were combined and washed with water (2×50 mL), 25 mL of brine, dried over MgSO4 and concentrated. The crude diester was diluted with 120 mL of H2O and 18 g (320 mmol) of KOH was added. The orange reaction mixture was stirred at 90° C. for 1.5 h, and washed with 2×30 mL of ether. Decarboxylation was effected by adjusting the pH to 1 with concentrated HCl and warming to 90° C. for 45 minutes. The pH of the solution was monitored and additional HCl was added as needed to maintain the pH of the solution below 2. The two phase system was extracted with 3×75 mL of ether and the combined ether layers were washed with 25 mL of H2O, 25 mL of brine, dried over MgSO4 and concentrated leaving 12.3 g (73.8%) of a white solid which was not purified, but directly resolved into individual enantiomers.
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[NH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14]>>[C:1]([NH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: NCCCCCC(=O)O
Reactant: C=C(C)C(=O)Cl
Product: C=C(C)C(=O)NCCCCCC(=O)O

Procedure:
Methacryloyl chloride was reacted with 6-amino caproic acid to give N-methacryloyl 6-amino caproic acid. This was then esterified with p-nitrophenol using standard synthetic methods to give N-methacryloyl 6-amino caproyl p-nitrophenol. 0.5 gm (0.0018 mol) N-isobutyryl 6-amino osproyl 2-amino pyridine, 0.4 gm N-methacryloyl histidine and 0.1071 gm CoCl2.6H2O were dissolved in 5 ml methanol and stirred for 1 hour. Methanol was then removed under reduced pressure. This was further diluted with 3.5 gm 2-hydroxyethyl methacrylate and 0.5 ml ethylene glycol dimethacrylate, and 100 mg azobisisobutyronitrile.