Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]([CH2:20][CH:21]=[CH:22][C:23]([N:25]2[CH:29]([CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:28][O:27][C:26]2=[O:37])=[O:24])[O:10][C:9]1([CH3:39])[CH3:38])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[O:42][C:43]([CH:45]=[CH2:46])=[CH2:44].[Cl-].C([Al+]CC)C.C1(C)C=CC=CC=1>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]([CH2:20][CH:21]2[CH2:44][C:43](=[O:42])[CH2:45][CH2:46][CH:22]2[C:23]([N:25]2[CH:29]([CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:28][O:27][C:26]2=[O:37])=[O:24])[O:10][C:9]1([CH3:39])[CH3:38])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1C(Cc2ccccc2)C(CC=CC(=O)N2C(=O)OCC2Cc2ccccc2)OC1(C)C
Reactant: C=CC(=C)O[Si](C)(C)C
Agent: CC[Al+]CC
Agent: [Cl-]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1C(Cc2ccccc2)C(CC2CC(=O)CCC2C(=O)N2C(=O)OCC2Cc2ccccc2)OC1(C)C
Temperature: -78 °C
Reaction time: 48 h

Procedure:
A solution of 4-Benzyl-5-[4-(-4-benzyl-2-oxo-oxazolidin-3-yl)-4-oxo-but-2-enyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (13.35 g, 25 mmol) in dichloromethane (500 ml) was stirred at −78° C. under nitrogen during the addition of 2-trimethylsiloxy-1,3-butadiene (26 ml, 150 mmol) and 1.8 M diethylaluminium chloride solution in toluene (70 ml, 125 mmol). The resulting pale yellow solution was stirred at −78° C. for 48 hours then slowly added to vigorously stirred, ice-cold 1 M hydrogen chloride aqueous solution. After 1 hour the two layers were separated and the aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium hydrogen carbonate solution and brine, dried (anhydrous magnesium sulfate) and concentrated in vacuo to give, after purification by flash chromatography on silica gel (ethyl acetate/hexane 1/9 to 4/6), 4-Benzyl-5-[2-(4-benzyl-2-oxo-oxazolidine-3-carbonyl)-5-oxo-cyclohexylmethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (8.7 g) as a white foam.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:32])[C:19]3[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([N+:29]([O-])=O)[CH:20]=3)[CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH:5]=[N:4][CH:3]=1.[Cl-].[NH4+].[In]>C(O)C.O>[NH2:29][C:21]1[CH:20]=[C:19]([CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=1)[C:18]([NH:17][C:13]1[CH:14]=[CH:15][CH:16]=[C:11]([C@@H:9]([NH:8][C:6]2[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[N:7]=2)[CH3:10])[CH:12]=1)=[O:32]
Reactant: C[C@H](Nc1cncc(Cl)n1)c1cccc(NC(=O)c2cc([N+](=O)[O-])cc(C(F)(F)F)c2)c1
Agent: [Cl-]
Agent: [In]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: C[C@H](Nc1cncc(Cl)n1)c1cccc(NC(=O)c2cc(N)cc(C(F)(F)F)c2)c1
Temperature: 25 °C
Yield: 64.5 %

Procedure:
To a solution of (S)—N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-3-nitro-5-(trifluoromethyl)benzamide (74 mg, 0.16 mmol) in ethanol (3 mL) was added a solution of ammonium chloride (85 mg, 1.6 mmol) in water (1.5 mL), then indium powder (73 mg, mesh 100, 0.64 mmol). The mixture was heated at reflux for 40 hours, was allowed to cool to room temperature and was filtered through Celite. The filter cake was washed with ethanol and the combined filtrates were concentrated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and water (30 mL), the phases separated and the organic phase washed with brine (30 mL), dried (Na2SO4) and concentrated under reduced pressure to give a yellow oil which was purified by flash chromatography (silica, ethyl acetate/hexanes) to give (S)-3-amino-N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-5-(trifluoromethyl)benzamide (45 mg, 65%) as a pale yellow solid.
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:31][C:32]3[CH:41]=[C:40]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])[C:39]([O:47][CH:48]([CH3:50])[CH3:49])=[CH:38][C:33]=3[C:34]=2[C:35]([NH2:37])=O)=[CH:26][CH:25]=1>C1COCC1>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:31][C:32]3[CH:41]=[C:40]([NH:42][S:43]([CH3:46])(=[O:44])=[O:45])[C:39]([O:47][CH:48]([CH3:49])[CH3:50])=[CH:38][C:33]=3[C:34]=2[C:35](=[S:10])[NH2:37])=[CH:26][CH:25]=1
Reactant: CC(C)Oc1cc2c(C(N)=O)c(-c3ccc(F)cc3)oc2cc1NS(C)(=O)=O
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1CCOC1
Product: CC(C)Oc1cc2c(C(N)=S)c(-c3ccc(F)cc3)oc2cc1NS(C)(=O)=O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 169.6 %

Procedure:
The reaction was run in two batches and combined for workup. In the first batch, Lawesson's reagent (27 mg, 0.067 mmol) was added to a solution of 2-(4-fluorophenyl)-5-isopropoxy-6-(methylsulfonamido)benzofuran-3-carboxamide (35 mg, 0.086 mmol) in THF (1.2 mL). The reaction was stirred at r.t. for 2 h, at which point additional Lawesson's reagent (8 mg, 0.020 mmol) was added. In the second batch, Lawesson's reagent (129 mg, 0.32 mmol) was added to a solution of 2-(4-fluorophenyl)-5-isopropoxy-6-(methylsulfonamido)benzofuran-3-carboxamide (125 mg, 0.31 mmol) in THF (3 mL) was stirred at r.t. for 1.5 h. The two batches were then combined and partitioned between EtOAc (50 mL) and water (10 mL). The organic phase was washed with sat'd NaHCO3 and brine, dried over Na2SO4, filtered, and concentrated to give a yellow oil. The residue was purified by silica gel chromatography (BIOTAGE® 25+S silica gel cartridge, gradient elution: 20% to 80% EtOAc/hexanes over 20 column volumes, fraction collection at λ=320 nm) to give 48 mg (29% yield) of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.76-7.87 (m, 2H) 7.71 (d, J=5.86 Hz, 2H) 7.53 (br. s., 1H) 7.13-7.23 (m, 2H) 6.97 (s, 1H) 6.90 (br. s., 1H) 4.74 (dt, J=12.08, 6.04 Hz, 1H) 2.93 (s, 3H) 1.40 (d, J=6.22 Hz, 6H). LC/MS was performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters MICROMASS®. LC/MS method: solvent A=5% CH3CN/95% H2O/0.1% NH4OAc, solvent B=95% CH3CN/5% H2O/0.1% NH4OAc, start % B=0, final % B=100, gradient time=2 min, stop time=3 min, flow rate=5 ml/min, column: XBridge C18 5 μm 4.6×50 mm; HPLC Rt=1.39 min, (ES+) m/z (MH+)=423.
Reaction SMILES: [CH3:1][NH:2][CH:3]1[CH2:6][CH2:5][CH2:4]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:14][CH2:15][CH2:16][Cl:17]>C(#N)C>[Cl:17][CH2:16][CH2:15][CH2:14][N:2]([CH3:1])[CH:3]1[CH2:6][CH2:5][CH2:4]1
Reactant: ClCCCBr
Reactant: CNC1CCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CN(CCCCl)C1CCC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 38.3 %

Procedure:
To a solution of N-methylcyclobutanamine (1 g, 3.89 mmol) and potassium carbonate (1.18 g, 8.56 mmol) in acetonitrile (20 ml) at 0° C. was added 1-bromo-3-chloropropane (383 μl, 3.89 mmol). Reaction was warmed to room temperature and stirred for 24 hours. Solid removed by filtration and filtrate concentrated in vacuo to give the title compound (241 mg, 38%) as an oil. No purification was performed. LRMS APCI+ m/z 162 [MH]+.
Reaction SMILES: Cl.[CH2:2]([N:4]([CH2:7][CH2:8][CH:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19]C)[CH:15]=2)[CH2:10]1)[CH2:5][CH3:6])[CH3:3].[OH-].[Na+].C(=O)([O-])[O-].[K+].[K+]>Br>[CH2:2]([N:4]([CH2:7][CH2:8][CH:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:19])[CH:15]=2)[CH2:10]1)[CH2:5][CH3:6])[CH3:3]
Reactant: CCN(CC)CCC1CCc2cc(OC)ccc2C1
Agent: Br
Agent: Cl
Agent: O=C([O-])[O-]
Product: CCN(CC)CCC1CCc2cc(O)ccc2C1
Yield: 104.2 %

Procedure:
(+)-2-[2-(N,N-Diethylamino)ethyl]-6-methoxytetralin hydrochloride (5.2 g) was added to 48% hydrobromic acid (10 ml) and the reaction mixture was heated under reflux for 4 hr and cooled. The reaction mixture was neutralized with 1 N aqueous sodium hydroxide followed by addition of 10% aqueous potassium carbonate and extracted with the combined solvent of ethyl acetate and THF (1:1). The organic layer was washed with saturated aqueous sodium chloride, dried, and concentrated. The residue was recrystallized from methanol-diisopropyl ether to obtain the titled compound (4.5 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH:11]([CH3:28])[CH2:12][C:13]2[CH:27]=[CH:26][C:16]3[O:17][C:18]([C:23]([OH:25])=[O:24])([C:20]([OH:22])=[O:21])[O:19][C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[C:30]12([CH2:40]O)[CH2:39][CH:34]3[CH2:35][CH:36]([CH2:38][CH:32]([CH2:33]3)[CH2:31]1)[CH2:37]2.Cl.[K+].[Br-]>C(Cl)(Cl)Cl>[C:30]12([CH2:40][O:24][C:23]([C:18]3([C:20]([O:22][CH2:40][C:30]45[CH2:39][CH:34]6[CH2:33][CH:32]([CH2:38][CH:36]([CH2:35]6)[CH2:37]4)[CH2:31]5)=[O:21])[O:17][C:16]4[CH:26]=[CH:27][C:13]([CH2:12][C@H:11]([NH:10][CH2:9][C@@H:8]([C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=5)[OH:29])[CH3:28])=[CH:14][C:15]=4[O:19]3)=[O:25])[CH2:39][CH:34]3[CH2:35][CH:36]([CH2:38][CH:32]([CH2:33]3)[CH2:31]1)[CH2:37]2
Reactant: CC(Cc1ccc2c(c1)OC(C(=O)O)(C(=O)O)O2)NCC(O)c1cccc(Cl)c1
Reactant: OCC12CC3CC(CC(C3)C1)C2
Agent: Cl
Agent: [Br-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: C[C@H](Cc1ccc2c(c1)OC(C(=O)OCC13CC4CC(CC(C4)C1)C3)(C(=O)OCC13CC4CC(CC(C4)C1)C3)O2)NC[C@H](O)c1cccc(Cl)c1

Procedure:
The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and adamantan-1-ylmethanol according to the procedure of Example 1 as a white solid (HCl salt); 1H NMR (CDCl3) δ 1.25 (m, 2H), 1.35 (d, 3H), 1.51 (s, 12H), 1.55-1.61 (m, 2H), 1.61-1.67 (m, 4H), 1.67-1.75 (m, 6H), 1.97 (s, 4H), 3.20 (s, 2H), 3.42-3.49 (m, 2H), 3.88 (s, 4H), 4-11-4.16 (q, 1H), 5.45 (bd, 1H), 5.65 (bd, 1H), 6.75 (m, 1H), 6.78-6.89 (m, 2H), 7.23-7.30 (m, 3H), 7.44 (s, 1H), 8.74 (bs, 1H), 10.115 (bs, 1H); IR (KBr) 3418 cm-1 (--OH), 1767 cm-1 (C=O); MS (ES) m/z 718.4 (MH+); [α]D25 -15° (c, 1.0, CHCl3). Anal. Calcd. for C42H52ClNO7 : C, 68.94; H, 9.22; N, 1.90; Cl, 9.40. Found: C, 67.48; H, 7.49; N, 1.48; Cl, 8.10.
Reaction SMILES: [CH2:1]([NH:5]/[C:6](/[CH3:12])=[CH:7]\[C:8]([O:10][CH3:11])=[O:9])[CH2:2][CH2:3][CH3:4].Cl.CO.N/C(/C)=C\C(OC)=O.FC(F)(F)CO>>[CH2:1]([NH:5][CH:6]([CH3:12])[CH2:7][C:8]([O:10][CH3:11])=[O:9])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN/C(C)=C\C(=O)OC
Agent: COC(=O)/C=C(/C)N
Agent: Cl
Solvent: OCC(F)(F)F
Solvent: CO
Product: CCCCNC(C)CC(=O)OC
Reaction time: 15 h
Yield: 10.6 %

Procedure:
The reaction was carried out in a manner similar to that in Example 9, except that 26.2 mg (0.0292 mmol) of Ru(OCOCH3)2((S)-tol-binap), 0.500 mg (2.92 mmol) of methyl 3-(n-butylamino)crotonate and 2.5 ml of 10% hydrogen chloride-methanol solution were used instead of 78.0 mg (0.0869 mmol) of Ru(OCOCH3)2((S)-tol-binap), 1.00 g (8.69 mmol) of methyl 3-aminocrotonate and 5 ml of 2,2,2-trifluoroethanol, respectively, and except that the reaction was carried out for 16 hours instead of 15 hours, and the reaction mixture was treated as in Example 9 to give methyl 3-(n-butylamino)butanoate in a yield of 10.6%.
Reaction SMILES: CO[C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10]Br.[C:13]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:18]=[CH:17][C:16]([CH2:19][NH2:20])=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[C:13]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:14]=[CH:15][C:16]([CH2:19][N:20]2[CH2:10][C:5]3[C:4](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:3]2=[O:12])=[CH:17][CH:18]=1
Reactant: COC(=O)c1ccccc1CBr
Reactant: NCc1ccc(-c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: O=C1c2ccccc2CN1Cc1ccc(-c2ccccc2)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 52.8 %

Procedure:
A mixture of 2-bromomethyl-benzoic acid methyl ester (0.115 g, 0.5 mmol), C-biphenyl-4-yl-methylamine (0.110 g, 0.6 mmol), and K2CO3 (0.207 g, 1.5 mmol) in toluene (3 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 2-biphenyl-4-ylmethyl-2,3-dihydro-isoindol-1-one (0.079 g, 53%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.26 (s, 2H), 4.84 (s, 2H), 7.32-7.56 (m, 12H), 7.89 (d, 1H). GC-MS: m/z 299 (M)+.
Reaction SMILES: C([O-])([O-])=O.[Ca+2].[C:6]([O:9][C@@H:10]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:26]2[CH2:25][CH2:24][C@@:23]2([CH3:31])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C:20](=[O:22])[CH3:21])[CH2:11]1)(=[O:8])[CH3:7].[C:32]([O:35][C@@H:36]1[CH2:57][CH2:56][C@@:55]2([CH3:58])[C@@H:38]([CH2:39][CH2:40][C@@H:41]3[C@@H:54]2[CH2:53][CH2:52][C@@:51]2([CH3:59])[C@H:42]3[CH2:43][CH2:44][C@@H:45]2[C:46]([OH:50])([C:48]#[N:49])[CH3:47])[CH2:37]1)(=[O:34])[CH3:33]>C1CCCCC1>[C:6]([O:9][C@@H:10]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C@@H:12]([CH2:13][CH2:14][C@@H:15]3[C@@H:26]2[CH2:25][CH2:24][C@@:23]2([CH2:31][C:48]#[N:49])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C:20](=[O:22])[CH3:21])[CH2:11]1)(=[O:8])[CH3:7].[C:32]([O:35][C@@H:36]1[CH2:57][CH2:56][C@@:55]2([CH3:58])[C@@H:38]([CH2:39][CH2:40][C@@H:41]3[C@@H:54]2[CH2:53][CH2:52][C@@:51]2([CH3:59])[C@H:42]3[CH2:43][CH2:44][C@@H:45]2[C:46](=[O:50])[CH3:47])[CH2:37]1)(=[O:34])[CH3:33]
Reactant: CC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](C(C)(O)C#N)CC[C@@H]32)C1
Agent: CC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(C)[C@@H](C(C)=O)CC[C@@H]32)C1
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: C1CCCCC1
Product: CC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2CC[C@]2(CC#N)[C@@H](C(C)=O)CC[C@@H]32)C1

Procedure:
Compound 8a was prepared using a reported procedure. (See, Kalvoda, J., et al., Reactions of Steroid Hypoiodites. VII. 1,4-Shift of the Nitrile Group (18-Cyanopregnanes), Helv. Chim. Acta 1966, 49: 424-436)12 (1.6 g, 6.30 mmol) was added to a refluxing mixture of Pb(OAc)4 (6.0 g, 13.5 mmol) and CaCO3 (2 g, 20.0 mmol) in cyclohexane (200 mL). The purple solution was refluxed for 1 h and the mixture of compound 6a and 7a obtained in last step [prepared from 6a (1.0 g, 2.77 mmol)] was added. The reaction mixture was refluxed while irradiated with a 300 W tungsten lamp for 3 h and then cooled to room temperature. After filtration, the precipitate was washed thoroughly with ether. The combined filtrate was washed successively with 10% Na2S2O3 and brine, and dried over Na2SO4. Removal of solvent under reduced pressure gave a residue which was purified by column chromatography (silica gel; hexanes/EtOAc, 4:1) to give compound 8a (400 mg, 40% from 6a) and recovered compound 6a (400 mg).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10](=O)[CH3:11].[NH2:13][NH2:14].C([O-])(=O)C.[Na+]>C1(C)C=CC=CC=1>[CH3:9][O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]2[C:3]=1[C:10]([CH3:11])=[N:13][NH:14]2
Reactant: NN
Reactant: COc1cccc(F)c1C(C)=O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1cccc2[nH]nc(C)c12
Temperature: 135 °C

Procedure:
A solution of 1-(2-fluoro-6-methoxyphenyl)ethanone (1 g), hydrazine (1.04 g), and sodium acetate (0.49 g) was stirred for 72 hours in toluene (10 mL). The mixture was concentrated, taken up in DMSO (8 mL), and heated to 135° C. for 24 hours. The mixture was cooled, poured into ethyl acetate (200 mL), and rinsed with 3× water, and brine. The organic layer was concentrated and chromatographed on silica gel using 10-100% ethyl acetate/hexanes.
Reaction SMILES: [CH:1]([C:3]1[C:4]([NH:15][CH2:16][CH2:17][NH:18][C:19](=[O:21])[CH3:20])=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2)=[O:2].[BH4-].[Na+]>C1COCC1>[OH:2][CH2:1][C:3]1[C:4]([NH:15][CH2:16][CH2:17][NH:18][C:19](=[O:21])[CH3:20])=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2
Reactant: COc1ccc2nc(NCCNC(C)=O)c(C=O)cc2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc2nc(NCCNC(C)=O)c(CO)cc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93 %

Procedure:
To a stirred solution of N-(2-(3-formyl-6-methoxyquinolin-2-ylamino)ethyl)acetamide SLA 41168 (0.70 g, 2.43 mmol) in THF (30 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added NaBH4 (0.09 g, 2.43 mmol) and the mixture was stirred overnight at RT then cooled in an ice bath before quenching by addition of a 1 N aq. HCl solution (40 mL). After stirring for 15 min, the mixture was basified to pH=9 using a 2 N aq. NaOH solution. THF was removed at 40° C. under vacuum and the solution was extracted with CH2Cl2 (200 mL), washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to give N-(2-(3-(hydroxymethyl)-6-methoxyquinolin-2-ylamino)ethyl)acetamide SLA 41174 as an orange solid (0.65 g, 93% yield).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH:19]([CH2:21][CH3:22])[CH3:20])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6].[N:23]([O-])=[O:24].[Na+]>C(O)=O>[Cl:1][CH2:2][CH2:3][N:4]([N:23]=[O:24])[C:5]([N:7]([CH:19]([CH2:21][CH3:22])[CH3:20])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@H:13]([OH:14])[C@H:11]([OH:12])[C@H:9]1[OH:10])=[O:6]
Reactant: CCC(C)N(C(=O)NCCCl)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O=CO
Product: CCC(C)N(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O
Reaction time: 1 h
Yield: 22.4 %

Procedure:
7.0 g of 1-(2-chloroethyl)-3-sec.butyl-3-D-galactopyranosylurea are dissolved in 20 ml of formic acid, and 5.0 g of sodium nitrite are added gradually thereto at 0° to 5° C. for one hour under stirring. The mixture is further stirred at the same temperature for one hour. After the reaction, the mixture is treated in the same manner as described in Example 5-(2). 1.7 g of 1-(2-chloroethyl)-1-nitroso-3-sec.butyl-3-D-galactopyranosylurea are thereby obtained as pale yellow caramel.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:10][NH:11][CH:12]=[O:13])[CH:7]=[CH:8][CH:9]=1)([O-])=O.NC1C=CC(NNC=O)=CC=1>>[NH2:1][C:4]1[CH:5]=[C:6]([NH:10][NH:11][CH:12]=[O:13])[CH:7]=[CH:8][CH:9]=1
Reactant: O=CNNc1cccc([N+](=O)[O-])c1
Agent: Nc1ccc(NNC=O)cc1
Product: Nc1cccc(NNC=O)c1

Procedure:
By reacting 2-(3-nitrophenyl)-1-formylhydrazine in an analogous manner as in (2), 21.0 g of 2-(3-aminophenyl)-1-formylhydrazine was obtained. Melting point: 108° to 113° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[NH:11][C:12]1C=[C:16]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:14][N:13]=1.O.[NH2:25]N>CO.C(OCC)(=O)C>[CH3:1][C:2]1[C:3]([NH:11][C:12]2[N:25]=[C:16]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[CH:15]=[CH:14][N:13]=2)=[CH:4][C:5]([NH2:8])=[CH:6][CH:7]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1Nc1cc(-c2cccnc2)ccn1
Reactant: NN
Solvent: CCOC(C)=O
Solvent: O
Solvent: CO
Product: Cc1ccc(N)cc1Nc1nccc(-c2cccnc2)n1
Temperature: 80 °C
Yield: 56.4 %

Procedure:
N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl)pyridine-2-amine (3.07 g, 10.0 mmol), hydrazine monohydrate (1.54 g of 65% solution in water, 20.0 mmol), FeCl3 (21 mg, 0.13 mmol), and activated carbon (0.2 g) were dissolved in a mixture of methanol (200 mL) and ethyl acetate (100 mL). The reaction mixture was heated to 80° C. with stirring and maintained for 24 hours. The reaction mixture was cooled own to room temperature. The insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in ethyl acetate (150 mL) and washed with water (150×2). The organic phase was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resulting residue was purified by column chromatography (biotage: DMC/Methanol, 1-8%, 25 CV). The product was obtained (1.57 g, yield: 56.4%) as a yellow solid and 0.53 g starting material of N-(2-methyl-5-nitrophenyl)-4-(pyridine-3-yl)pyridine-2-amine was recovered; 1H NMR (500 MHz, CDCl3) δ 2.28 (s, 3H), 3.68 (s, 2H), 6.45 (d, 1H), 6.95 (s, 1H), 7.02 (d, 1H), 7.18 (d, 1H), 7.45 (m, 1H), 7.35 (d, 1H), 7.65 (s, 1H), 8.37 (d, 1H), 8.52 (d, 1H), 8.74 (d, 1H), 9.28 (s, 1H). LC-MS (m/z) calculated, 277.3. found, 278.2 [M+H]+.
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([OH:12])[CH:9]=[C:8]([OH:13])[CH:7]=1)[CH:2]=[CH2:3].O[C:16]1C=C(C=C(O)C=1C)C(O)=O>>[CH2:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([OH:12])[C:9]([CH3:16])=[C:8]([OH:13])[CH:7]=1)[CH:2]=[CH2:3]
Reactant: Cc1c(O)cc(C(=O)O)cc1O
Reactant: C=CCOC(=O)c1cc(O)cc(O)c1
Product: C=CCOC(=O)c1cc(O)c(C)c(O)c1

Procedure:
This compound was prepared analogously to 3,5-Dihydroxy-benzoic acid allyl ester [Example 1(a)], however 3,5-dihydroxy-4-methylbenzoic acid was used instead of 3,5-dihydroxybenzoic acid.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11](Cl)=[O:12])[CH2:8]2)=[CH:4][CH:3]=1.[OH-].[NH4+:17]>O1CCCC1.O>[Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH:7]2[CH2:10][N:9]([C:11]([NH2:17])=[O:12])[CH2:8]2)=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: O=C(Cl)N1CC(Oc2ccc(Br)cc2)C1
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)N1CC(Oc2ccc(Br)cc2)C1
Reaction time: 18 h
Yield: 87.6 %

Procedure:
A stirred solution of 5.8 g (0.02 mole) of 3-(4-bromophenoxy)-1-azetidinecarbonyl chloride in 20 ml of tetrahydrofuran was treated with 3.8 g (4 ml) (0.06 mole) of 57% ammonium hydroxide. After stirring for 18 hr, the reaction mixture was diluted with 200 ml of water and the solid which separated was collected by filtration, 5.3 g. Recrystallization from ethanol-water yielded 4.75 g (87.6%) of fine white crystals, m.p. 193°-194° C.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:12]N(C)C=O.CN(C1C=CC=CN=1)C.C(N=C=NCCCN(C)C)C>CO.C(Cl)(Cl)Cl>[CH3:12][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([CH3:11])=[N:10][C:2]=1[Cl:1]
Reactant: Cc1ccc(C(=O)O)c(Cl)n1
Reactant: CN(C)C=O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COC(=O)c1ccc(C)nc1Cl
Temperature: 25 °C
Reaction time: 6 h

Procedure:
2-Chloro-6-methylnicotinic acid (25.0 g) was suspended in a mixed solvent of dimethylformamide (100 mL) and chloroform (100 mL), and to this suspension were added dimethylaminopyridine (21.3 g) and methanol (4.67 g). Finally, 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (WSC) hydrochloride (33.5 g) was added to the mixture, followed by stirring at room temperature for 6 hours. After the reaction mixture was concentrated, ethyl acetate (300 mL) was added thereto. The mixture was washed successively with water, 10% ammonium chloride, water, and saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=1:4, v/v) to give the title compound (24.6 g) as a colorless oil.
Reaction SMILES: C([O:3][C:4]([CH2:6][CH:7]1[O:12][CH2:11][CH2:10][N:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8]1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.O>C(OCC)C>[OH:3][CH2:4][CH2:6][CH:7]1[O:12][CH2:11][CH2:10][N:9]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:8]1
Reactant: CCOC(=O)CC1CN(Cc2ccccc2)CCO1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCOCC
Product: OCCC1CN(Cc2ccccc2)CCO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
A solution of 2-ethoxycarbonylmethyl-4-benzylmorpholine (41 g) in diethyl ether (100 ml) is added dropwise to a stirred suspension of lithium aluminum hydride (59.2 g) in diethyl ether (150 ml). The reaction mixture is stirred at 25° C. for 1 hour. The excess of lithium aluminum hydride is decomposed by the successive addition of ethyl acetate and water. The insoluble materials are filtered off, and the filtrate is evaporated to give the title compound (34.4 g) as an oil. The starting material, 2-ethoxycarbonylmethyl-4-benzylmorpholine, is prepared according to the method of F. Loftus [Syn. Commun., 10, 59-73 (1980)].