Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]=[C:9]=[S:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH2:11]([NH2:19])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>C1C=CC=CC=1>[CH2:1]([NH:8][C:9]([NH:19][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[S:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCCN
Reactant: CCCCCCCN=C=S
Solvent: c1ccccc1
Product: CCCCCCCCNC(=S)NCCCCCCC
Yield: 105.2 %

Procedure:
To a solution of 3.14 grams (0.02 mole) n-heptylisothiocyanate dissolved in 15 milliliters of benzene is added 2.58 grams (0.02 mole) n-octylamine. The temperature rose to 41° C. The mixture was then refluxed on a steam-bath for about 20 minutes, until the mixture reached a neutral pH. The solution was then evaporated under vacuum. A yield of 6.03 grams of 1-n-heptyl-3-n-octylthiourea was obtained.
Reaction SMILES: NC1N=C(N)C2C(=NC=C(CN(C3C=CC=CC=3)C3C=CC=CC=3)N=2)N=1.[CH:27]1[C:37]2[C:31](=[N:32][C:33]3[CH:41]=[CH:40][CH2:39][CH2:38][C:34]=3[CH2:35][CH:36]=2)[CH:30]=[CH:29][CH:28]=1.[H-].[Na+].Br.[NH2:45][C:46]1[N:47]=[C:48]([NH2:58])[C:49]2[CH:55]=[C:54]([CH2:56]Br)[CH:53]=[N:52][C:50]=2[N:51]=1>>[NH2:45][C:46]1[N:47]=[C:48]([NH2:58])[C:49]2[CH:55]=[C:54]([CH2:56][CH:38]3[C:34]4[CH2:35][CH:36]=[C:37]5[CH:27]=[CH:28][CH:29]=[CH:30][C:31]5=[N:32][C:33]=4[CH:41]=[CH:40][CH2:39]3)[CH:53]=[N:52][C:50]=2[N:51]=1
Reactant: Nc1nc(N)c2cc(CBr)cnc2n1
Reactant: C1=CC2=C(CC=c3ccccc3=N2)CC1
Agent: Br
Agent: Nc1nc(N)c2nc(CN(c3ccccc3)c3ccccc3)cnc2n1
Agent: [H-]
Product: Nc1nc(N)c2cc(CC3CC=CC4=C3CC=c3ccccc3=N4)cnc2n1

Procedure:
9-[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl]-9,10-dihydrodibenz-[b,f]azepine (Formula I: Ar=2,4-diaminopyrido[2,3-d]pyrimidin-6-yl; W=CH2; X=N; Z=CH2=CH2; m=n=0) is prepared similarly to N-[(2,4-diaminopteridin-6-yl)methyl]-N,N-diphenylamine as disclosed above by using 9,10-dihydrodibenz[b,f]azepine (158 mg, 0.8 mmol), NaH (50 mg, 2.1 mmol) and 2,4-diamino-6-bromomethylpyrido[2,3-d]pyrimidine hydrobromide (100 mg, 0.3 mmol). The product can be purified by chromatography.
Reaction SMILES: [OH:1][C:2]([CH3:12])([CH3:11])[CH2:3][C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1.[Br:13]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:13][C:9]1[CH:8]=[CH:7][C:6]([OH:10])=[CH:5][C:4]=1[CH2:3][C:2]([OH:1])([CH3:12])[CH3:11]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(O)Cc1cccc(O)c1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(O)Cc1cc(O)ccc1Br
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Alcohol 29 (12.3 g, 74.2 mmol) is dissolved in dry DMF and cooled to 0° C. under N2. Solid N-bromosuccinimide (NBS, 14.77 g, 83.0 mmol) is added in small portions (the yellow color is allowed to dissipate between additions) over 1.5 h. After the addition is complete, stirring at 0° C. is continued for 30 min. The mixture is then poured into water and extracted with EtOAc (3×). The organic phase is washed with water (1×) and brine (1×), dried (MgSO4), filtered, and evaporated. The residue is dissolved in EtOAc/CH2Cl2 and diluted with hexane to afford 30 as white crystals, mp 139-141° C. (12.7 g, 70%). Concentration of the mother liquor gives two more crops (1.2 and 1.0 g) of crystals, bringing the total to 14.9 g (82%). 1H NMR (acetone-d6, 2.05 ppm) 8.43 (S,1), 7.34 (d, 1, J=8.7), 7.01 (d, 1, J=2.7), 6.64 (dd, 1, J=8.7, 2.8), 2.89 (s,2), 1.21 (s,6); 13C NMR (acetone-d6, 20.83 ppm) 147.90, 130.98, 124.56, 111.34, 107.05, 106.19, 62.35, 39.59, 20.76; MS (EI, eE=70 eV) m/z 246/244 (M+), 231/229, 201, 188/186, 163, 150, 131, 108, 107, 91, 77, 63, 59 (base peak), 51, 43; Anal. Calcd for C10H13BrO2 (MW=245.1) : C,49.00 H,5.35. Found: C,49.03 H,5.20.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][OH:4].[OH:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[C:11]([C:17](Cl)=[O:18])[C:12](=[O:16])[O:13]2)=[CH:8][CH:7]=1>O1CCOCC1>[OH:4][CH2:3][CH2:2][NH:1][C:17]([C:11]1[C:12](=[O:16])[O:13][C:14]2[C:9]([CH:10]=1)=[CH:8][CH:7]=[C:6]([OH:5])[CH:15]=2)=[O:18]
Reactant: NCCO
Reactant: O=C(Cl)c1cc2ccc(O)cc2oc1=O
Solvent: C1COCCO1
Product: O=C(NCCO)c1cc2ccc(O)cc2oc1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 52.2 %

Procedure:
To a cold, stirred solution of 3.05 grams (g) [0.05 mole (mol)] of 2-aminoethanol in 30 milliliters (ml) of dioxane was added a suspension of 2.2 g (0.01 mol) of 7-hydroxycoumarin-3-carbonyl chloride [Sherman et al, Anal. Chem. 40:803(1968)] in 75 ml of dioxane. The mixture was stirred at 0° C. for 30 minutes, during which time a thick oil precipitated that solidified upon scratching with a spatula. The dioxane was decanted and the precipitate dissolved in water. Adjustment of the pH of the aqueous solution to 7.0 with glacial acetic acid resulted in precipitation of a tan solid. The solid precipitate was recrystallized from water to give 1.3 g (52% yield) of N-(2-hydroxyethyl)-7-hydroxycoumarin-3-carboxamide as a white solid with a melting point of 244°-245° C. Elemental analysis and infrared spectral data for the product are given below:
Reaction SMILES: [C:1]([NH2:5])([CH3:4])([CH3:3])[CH3:2].[Cl:6][C:7]1[CH:12]=[N:11][CH:10]=[C:9](Cl)[N:8]=1.C(OC(O)C)C>CCN(C(C)C)C(C)C>[C:1]([NH:5][C:9]1[CH:10]=[N:11][CH:12]=[C:7]([Cl:6])[N:8]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Clc1cncc(Cl)n1
Reactant: CC(C)(C)N
Agent: CCOC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)Nc1cncc(Cl)n1
Temperature: 130 °C

Procedure:
A mixture of tert-butylamine (14.9 g, 20 mmol), 2,6-dichloropyrazine (6.0 g, 40 mmol), Hünig's base (10 mL) and ethoxyethanol (6 mL) was heated at 130° C. in a sealed tube for 18 hours. The solvent was removed in vacuo and the residue taken up in CH2Cl2 (100 mL) and filtered. The filtrate was washed with H2O (2×20 mL), brine (20 mL) and dried (Na2SO4). Chromatography eluting with CH2Cl2 separated the product as a white solid (5.4 g, 72%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][NH:4][N:5]=[C:6]([C:14]1[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.[CH3:21][C:22]([Si:25](Cl)([CH3:27])[CH3:26])([CH3:24])[CH3:23].N1C=CN=C1.O>CN(C=O)C>[CH3:21][C:22]([Si:25]([CH3:27])([CH3:26])[O:1][CH2:2][CH2:3][NH:4][N:5]=[C:6]([C:14]1[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=1)[CH2:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCNN=C(Cc1ccncc1)c1ccc(F)cc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCNN=C(Cc1ccncc1)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98 %

Procedure:
To a solution of the 1-(4-fluorophenyl)-2-(4-pyridinyl) ethanone (2-hydroxyethyl)hydrazone prepared in step 1 (2.73 g, 0.01 mol) and (1,1-dimethylethyl) dimethylsilyl chloride (1.5 g, 0.01 mol) in 25 mL of DMF was added imidazole portionwise. The reaction mixture was stirred at room temperature overnight. Water was added and extracted with ethyl acetate, the organic layer was washed with water, washed with brine, dried over magnesium sulfate and filtered. The filtrate was concentrated to give 3.8 g of crude product, 1-(4-fluorophenyl)-2-(4-pyridinyl)ethanone [2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethyl]hydrazone, as a yellow oil that was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]([CH3:12])([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=O.C(Cl)(=O)C(Cl)=O.[CH3:19][C:20]1[C:24]([CH3:25])=[C:23]([NH:26][S:27]([C:30]2[C:31]([C:36]3[CH:41]=[CH:40][C:39]([C:42]4[O:43][CH:44]=[CH:45][N:46]=4)=[CH:38][C:37]=3[CH2:47][NH:48][CH3:49])=[CH:32][CH:33]=[CH:34][CH:35]=2)(=[O:29])=[O:28])[O:22][N:21]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[CH3:19][C:20]1[C:24]([CH3:25])=[C:23]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]2[CH:41]=[CH:40][C:39]([C:42]3[O:43][CH:44]=[CH:45][N:46]=3)=[CH:38][C:37]=2[CH2:47][N:48]([CH3:49])[C:3](=[O:5])[C:2]([CH3:1])([CH3:12])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)(=[O:29])=[O:28])[O:22][N:21]=1
Reactant: CNCc1cc(-c2ncco2)ccc1-c1ccccc1S(=O)(=O)Nc1onc(C)c1C
Reactant: CC(C)(C(=O)O)c1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1noc(NS(=O)(=O)c2ccccc2-c2ccc(-c3ncco3)cc2CN(C)C(=O)C(C)(C)c2ccccc2)c1C
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To α,α-dimethylbenzeneacetic acid (16.4 mg, 0.1 mmol) and 0.003 ml DMF in 1 ml CH2Cl2, oxalyl chloride (2M in CH2 Cl2, 0.125 ml, 0.25 mmol) was added. The mixture was stirred at room temperature for 1 hr and 15 min and concentrated. The mixture, containing α,α-dimethylbenzeneacetyl chloride, was dissolved in 1 ml CH2Cl2 and cooled to 0° C., and N-(3,4-dimethyl-5-isoxazolyl)-2'-[(methylamino)methyl]-4'-(2-oxazolyl)[1,1'-biphenyl]-2-sulfonamide (33 mg, 0.075 mmol, prepared as described in Step (A) of Example 28) and triethylamine (23 mg, 0.225 mmol) were added. The reaction was stirred at room temperature for 40 min and concentrated. The residue was purified by preparative HPLC on an ODS S10 column using 18% solvent A (10% MeOH, 90% H2O, 0.1% TFA) and 82% solvent B (90% MeOH, 10% H2O, 0.1% TFA) to provide the title compound of this Example (20 mg, 46%) as a white solid, m.p. 130°-138° C. (amorphous).
Reaction SMILES: [CH3:1][C:2]([O:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][CH:11]=1)([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H][H]>[Pd].C(O)C>[NH2:16][C:13]1[CH:12]=[CH:11][C:10]([O:9][C:2]([CH3:1])([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:15][CH:14]=1
Reactant: [H][H]
Reactant: CCOC(=O)C(C)(C)Oc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)C(C)(C)Oc1ccc(N)cc1

Procedure:
A mixture of 50.6 g. (0.2 mol) ethyl 2-methyl-2-(4-nitrophenoxy)-propionate, 500 ml. ethanol and about 20 g. 5% palladium charcoal is hydrogenated in a shaker at ambient temperature and atmospheric pressure until the necessary amount of hydrogen has been taken up. The reaction mixture is subsequently filtered with suction and the liquid phase is evaporated to give a quantitative yield of crude ethyl 2-(4-aminophenoxy)-2-methylpropionate in the form of a distillable oil (b.p. 134°-135° C./0.05 mm.Hg.); nD20 =1.5035; m.p. of the hydrochloride 153°-154° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].Cl.[NH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C>Cl.NCCCCCCCCCCCC(OCC)=O>[N+:12]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:10][CH:9]=[CH:8][CH:7]=2)([O-:14])=[O:13]
Reactant: O=[N+]([O-])c1cnc2ccccc2c1Cl
Reactant: CCOC(=O)CCCCCCCCCCCN
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCN(CC)CC
Product: CCOC(=O)CCCCCCCCCCCNc1c([N+](=O)[O-])cnc2ccccc12
Reaction time: 6 h
Yield: 100.3 %

Procedure:
4-Chloro-3-nitroquinoline (15.52 g, 74.40 mmol) was treated with ethyl 12-aminododecanoate hydrochloride (25.0 g, 89.3 mmol) in the presence of potassium carbonate (10.28 g, 74.38 mmol) and triethylamine (25.9 mL, 186 mmol) according to a modification of the method described in Part A of Example 15. After the reaction was stirred for six hours, an analysis by TLC indicated the presence of starting material, and additional ethyl 12-aminododecanate hydrochloride (1.0 g, 3.6 mmol) was added. The reaction was stirred overnight and subjected to the work-up procedure to provide 31.0 g of ethyl 12-(3-nitroquinolin-4-ylamino)dodecanoate.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17](I)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1.[CH3:22][O:23][C:24]1[N:29]=[CH:28][C:27](B(O)O)=[CH:26][N:25]=1>C(=O)([O-])[O-].[K+].[K+].O.C(#N)C.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]>[NH2:1][C:2]1[C:3]([F:21])=[C:4]([C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([C:27]4[CH:26]=[N:25][C:24]([O:23][CH3:22])=[N:29][CH:28]=4)[CH:18]=3)[NH:13][CH:12]=2)=[O:10])[C:5]([F:8])=[CH:6][CH:7]=1
Reactant: Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(I)cc23)c1F
Reactant: COc1ncc(B(O)O)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: CC#N
Product: COc1ncc(-c2cnc3[nH]cc(C(=O)c4c(F)ccc(N)c4F)c3c2)cn1
Temperature: 160 °C
Yield: 43.6 %

Procedure:
In a microwave vial, (3-amino-2,6-difluoro-phenyl)-(5-iodo-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (19, 1.36 g, 3.41 mmol), 2-methoxy-pyrimidine-5-boronic acid (20, 1.05 g, 6.81 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.25 g, 0.34 mmol) were mixed in 22 mL of 1.00 M potassium carbonate in water and 18 mL of acetonitrile. The resulting mixture was heated at 160° C. in the microwave for 15 minutes. The resulting mixture was filtered through a thin layer of celite, and the celite bed was washed with a mixture of water and ethyl acetate. The two layers of the filtrate were separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum. The residue was purified by flash silica gel chromatography eluting with ethyl acetate and dichloromethane to provide the desired compound (21, 0.567 g). MS (ESI) [M+H+]+=382.1.
Reaction SMILES: C(OC(C1NN=C(COC2C=CC=CC=2)C=1)=O)C.CC1(C)OC[C@H](CO)N1C(OC(C)(C)C)=O.[C:35]([O:39][C:40]([N:42]1[C@H:46]([CH2:47][N:48]2[C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:51][C:50]([CH2:58][O:59][C:60]3[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=3)=[N:49]2)[CH2:45][O:44][C:43]1([CH3:67])[CH3:66])=[O:41])([CH3:38])([CH3:37])[CH3:36]>>[C:35]([O:39][C:40]([N:42]1[C@@H:46]([CH2:47][N:48]2[C:52]([C:53]([O:55][CH2:56][CH3:57])=[O:54])=[CH:51][C:50]([CH2:58][O:59][C:60]3[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=3)=[N:49]2)[CH2:45][O:44][C:43]1([CH3:66])[CH3:67])=[O:41])([CH3:36])([CH3:37])[CH3:38]
Reactant: CCOC(=O)c1cc(COc2ccccc2)nn1C[C@@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)N1[C@@H](CO)COC1(C)C
Agent: CCOC(=O)c1cc(COc2ccccc2)n[nH]1
Product: CCOC(=O)c1cc(COc2ccccc2)nn1C[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C

Procedure:
The compound was prepared from 5-phenoxymethyl-2H-pyrazole-3-carboxylic acid ethyl ester and (S)-1-boc-2,2-dimethyl-4-hydroxymethyl-oxazolidine using the method described in the preceding example 29 (R)-4-(5-ethoxycarbonyl-3-phenoxymethyl-pyrazol-1-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester.
Reaction SMILES: [N+:1]([C:4]1[CH:19]=[CH:18][CH:17]=[CH:16][C:5]=1[C:6]([CH:8]1[C:13](=O)[CH2:12][CH2:11][CH2:10][C:9]1=[O:15])=O)([O-:3])=[O:2].O.[NH2:21][NH2:22]>C(O)C>[O:15]=[C:9]1[CH2:10][CH2:11][CH2:12][C:13]2[NH:22][N:21]=[C:6]([C:5]3[CH:16]=[CH:17][CH:18]=[CH:19][C:4]=3[N+:1]([O-:3])=[O:2])[C:8]1=2
Reactant: O=C1CCCC(=O)C1C(=O)c1ccccc1[N+](=O)[O-]
Reactant: NN
Solvent: CCO
Solvent: O
Product: O=C1CCCc2[nH]nc(-c3ccccc3[N+](=O)[O-])c21
Yield: 44.9 %

Procedure:
3.2 g (12.2 mmol) of 2-nitrobenzoylcyclohexane-1,3-dione and 0.52 g (12.2 mmol) of hydrazine hydrate (80%) are refluxed for 4 hours in 120 ml of ethanol. The ethanol is subsequently distilled off under reduced pressure, and 80 ml of methanol are added. The solid which precipitates is filtered off with suction and dried in vacuo. 1.41 g (45% of theory) of 4,5,6,7-tetrahydro-4-oxo-3-(2-nitro-phenyl)-1H-indazole of the formula ##STR6## and of melting point 236° C. (decomp.) are obtained.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([OH:12])=[C:8]([CH:11]=1)[CH:9]=[O:10])[CH3:2].Br[CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([O:12][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:8]([CH:9]=[O:10])[CH:11]=1)[CH3:2]
Reactant: CCOC(=O)CCCCBr
Reactant: CCOc1ccc(O)c(C=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCOC(=O)CCCCOc1ccc(OCC)cc1C=O

Procedure:
2.49 g of 5-ethoxy-2-hydroxy-benzaldehyde, 2.7 ml of ethyl 5-bromovalerate, 15 ml of DMSO, 3.1 g of K2CO3 and 75 mg of KI were stirred for 2.5 hrs. at 55° C. After working up and chromatography on silica gel there were obtained 4.7 g of ethyl 5-(4-ethoxy-2-formyl-phenoxy)-pentanoate. MS: 294 (M)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23](=O)[CH2:24][O:25][C:26]2[C:31]([O:32][CH3:33])=[CH:30][CH:29]=[CH:28][C:27]=2[O:34][CH3:35])=[C:18]([CH3:37])[C:17]=1[CH3:38].Cl.[OH-].[Na+]>O1CCCC1>[CH3:33][O:32][C:31]1[CH:30]=[CH:29][CH:28]=[C:27]([O:34][CH3:35])[C:26]=1[O:25][CH2:24][CH2:23][NH:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[C:17]([CH3:38])[C:18]=1[CH3:37]
Reactant: COc1cc2nccc(Oc3ccc(NC(=O)COc4c(OC)cccc4OC)c(C)c3C)c2cc1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1cc2nccc(Oc3ccc(NCCOc4c(OC)cccc4OC)c(C)c3C)c2cc1OC
Temperature: 0 °C
Yield: 80.2 %

Procedure:
N1-{4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylphenyl}-2-(2,6-dimethoxyphenoxy)acetamide (200 mg) was dissolved in tetrahydrofuran (10 ml) to prepare a solution. A 1 M solution (1.3 ml) of a borane-tetrahydrofuran complex in tetrahydrofuran was then added to the solution, and the mixture was stirred with heating under reflux for 2 hr. The reaction solution was cooled to 0° C. and was adjusted to pH=1 by the addition of 1 N hydrochloric acid, followed by stirring with heating under reflux for 30 min. The reaction solution was cooled to 0° C., was adjusted to pH=12 by the addition of a 1 N aqueous sodium hydroxide solution, and was extracted with chloroform. After the concentration of the extract, the residue was purified on a column using chloroform/methanol to give the title compound (156 mg, yield 80%).
Reaction SMILES: [H-].[Na+].Cl[C:4]1[N:5]([CH2:12][C@:13]([OH:20])([CH3:19])[CH2:14][O:15][CH2:16][O:17][CH3:18])[CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[N:8]=1>CN(C=O)C>[CH3:18][O:17][CH2:16][O:15][CH2:14][C@:13]1([CH3:19])[O:20][C:4]2=[N:8][C:7]([N+:9]([O-:11])=[O:10])=[CH:6][N:5]2[CH2:12]1
Reactant: COCOC[C@](C)(O)Cn1cc([N+](=O)[O-])nc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCOC[C@@]1(C)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 60.7 %

Procedure:
Sodium hydride (1.0 g, 25 mmol) was added to a solution of (R)-2-chloro-1-(2-hydroxy-3-methoxymethoxy-2-methylpropyl)-4-nitroimidazole prepared in Example 27 (6.0 g, 21 mmol) in DMF (30 ml) with cooling on ice-bath followed by stirring at room temperature for 1.5 hours. Ice-water was added to the reaction mixture, and the precipitates were filtered off and washed with water to afford (R)-2-methoxymethoxymethyl-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (3.1 g, yield 59%) as a yellow solid.
Reaction SMILES: [N+:1]([C:4]1[C:9]([N+:10]([O-])=O)=[CH:8][C:7]([OH:13])=[C:6]([O:14][CH3:15])[CH:5]=1)([O-:3])=[O:2].C(N)=O.N>O>[NH2:10][C:9]1[C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]([O:14][CH3:15])=[C:7]([OH:13])[CH:8]=1
Reactant: COc1cc([N+](=O)[O-])c([N+](=O)[O-])cc1O
Agent: N
Solvent: O
Solvent: NC=O
Product: COc1cc([N+](=O)[O-])c(N)cc1O
Temperature: 95 °C

Procedure:
A mixture consisting of 0.15 mol (32.1 g) of 4,5-dinitro-2-methoxyphenol, prepared in Example 2, 150 ml of formamide and 200 ml of 28% strength ammonia solution in water is heated to 95° C. for 8 hours in an autoclave. After the mixture is cooled, the expected product crystallizes. It is dissolved in the minimum quantity of dimethylformamide, and is then precipitated by adding water. It melts at 208° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:9][C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[N:7][C:6]=1[CH2:17][CH:18]([O:21][CH3:22])[O:19][CH3:20])=[O:4].[OH-].[Na+]>CCO>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]2[S:9][C:5]([C:3]([OH:4])=[O:2])=[C:6]([CH2:17][CH:18]([O:21][CH3:22])[O:19][CH3:20])[N:7]=2)=[CH:11][CH:12]=1
Reactant: COC(=O)c1sc(-c2ccc(Cl)cc2)nc1CC(OC)OC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COC(Cc1nc(-c2ccc(Cl)cc2)sc1C(=O)O)OC
Temperature: 0 °C
Reaction time: 8 h
Yield: 95.9 %

Procedure:
Mix 2-(4-chloro-phenyl)-4-(2,2-dimethoxy-ethyl)-thiazole-5-carboxylic acid methyl ester (3.6 g, 10.5 mmol) in EtOH (40 mL) and then add 2 M NaOH (6.8 mL). Stir the slurry mechanically overnight and then concentrate in vacuo. Dissolve the solid in water (40 mL), cool to 0° C., and adjust the pH to 5-6 with 1 N HCl (13 mL). Stir the slurry for 15 min, collect the precipitate, and wash the solid with water (4×20 mL). Dry the solid in a vacuum oven overnight to give 3.3 g (96%) of the title compound. ES/MS m/z (35Cl) 326.0 [M−1]−.
Reaction SMILES: [CH2:1]([C:8]1[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=1[C:10](O)=[Se:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.C(N(CC)CC)C>ClCCl>[CH3:17][C:18]1[CH:24]=[CH:23][C:21]([NH:22][C:10](=[Se:11])[C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=2[CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:20][CH:19]=1
Reactant: OC(=[Se])c1ccccc1Cc1ccccc1
Reactant: Cc1ccc(N)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(NC(=[Se])c2ccccc2Cc2ccccc2)cc1
Reaction time: 2 h

Procedure:
A suspension of 4 g (0.013 mol) 2-benzylselenobenzoic acid in 80 ml dichloromethane is cooled to 0°-5° C. and treated with stirring with 2 g (0.015 mol) chloromethylenedimethyliminium chloride (Vilsmeir's reagent) in one portion. After 1 hour a solution of 1.47 g (0.0137 mol) 4-methylaniline and 3 g (0.03 mol) triethylamine are added dropwise in the cold and stirring continued for 2 hours at room temperature. The solution is washed successively with
Reaction SMILES: [CH2:1]1[CH:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][NH:2]1.N1C2C(CCCC2)CC1.N1CCC2CCCC12.C1C2(CCCCC2)CCN1.C1C2(CCCC2)CCN1.N1CCC2(CC3CC2CC3)C1.N1CCC2(CC3CCC2CC3)C1.C12C3CC1(CC3)CCCN2.N1CCC2CCCCCC12.N1CCC2CC12.C1C2C(CCCC2)CN1.C1C2CCCC2CN1.N1C2C(CCC=C2)CC1.N1CCC2CC=CC12>>[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1
Reactant: C1CCC2CNCCC2C1
Agent: C1=CC2NCCC2C1
Agent: C1=CC2NCCC2CC1
Agent: C1CC2(CN1)CC1CCC2C1
Product: c1ccc2c(c1)CCNC2

Procedure:
decahydroisoquinoline (B); octahydroindole (C); octahydrocyclopenta[b]pyrrole (D); 2-azaspiro[4.5]decane (E); 2-azaspiro[4.4]nonane (F); spiro[bicyclo[2.2.1]heptane-2,3'-pyrrolidine] (G); spiro[bicyclo[2.2.2]octane-2,3'-pyrrolidine] (H); 2-azatricyclo[4.3.0.16,9 ]decane (I); decahydrocyclohepta[b]-pyrrole (J); hexahydrocyclopropa[b]pyrrole (K); octahydroisoindole (L); octahydrocyclopenta[c]pyrrole (M); 2,3,3a,4,5,7a-hexahydroindole (N); 1,2,3,3a,4,6a-hexahydrocyclopenta[b]pyrrole (O); all of which can optionally be substituted.