Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.CI.[H-].[Na+].[C:35](=O)([O-])O.[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:35][NH:1][C:2]1[C:3]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C([O-])O
Reactant: CC(C)(C)OC(=O)N(Cc1cccc(Nc2ncccc2N)c1)C(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CNc1cccnc1Nc1cccc(CN(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 96 h
Yield: 21 %

Procedure:
To a mixture of the compound (88.5 mg) obtained in Example 3, methyl iodide (15 μl) and dimethylformamide (2 ml), sodium hydride (content=60%; 10 mg) was added and the resulting mixture was stirred at room temperature for 4 days. To the reaction mixture, ethyl acetate and a saturated aqueous sodium hydrogencarbonate solution were added. The organic layer was washed with a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:3) to give 19.3 mg of the titled compound (yield, 21%).
Reaction SMILES: C1(S([CH2:10][C:11]2[N:12]=[C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[NH:14][N:15]=2)(=O)=O)C=CC=CC=1.[CH3:22][C:23]1[CH:28]=[C:27](/[CH:29]=[CH:30]\[C:31]#[N:32])[CH:26]=[CH:25][N:24]=1>>[CH3:22][C:23]1[CH:28]=[C:27]([C:29]2[CH:30]=[C:31]([NH2:32])[N:15]3[N:14]=[C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=4)[N:12]=[C:11]3[CH:10]=2)[CH:26]=[CH:25][N:24]=1
Reactant: Cc1cc(/C=C\C#N)ccn1
Reactant: O=S(=O)(Cc1n[nH]c(-c2ccccn2)n1)c1ccccc1
Product: Cc1cc(-c2cc(N)n3nc(-c4ccccn4)nc3c2)ccn1

Procedure:
The title compound, MS m/e (%):303 (M+H+,100), was prepared in accordance with the general method of example 1 from 2-(5-benzenesulfonylmethyl-2H-[1,2,4]triazol-3-yl)-pyridine and (E)/(Z)-3-(2-methyl-pyridin-4-yl)-acrylonitrile.
Reaction SMILES: C([O:8][C:9]1[C:14]([C:15]#[C:16][CH2:17][CH2:18][CH2:19][N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])=[CH:13][N:12]=[C:11]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=2)[N:10]=1)C1C=CC=CC=1.FC(F)(F)C(O)=O>>[F:38][C:34]1[CH:33]=[C:32]([NH:31][C:11]2[N:10]=[C:9]([OH:8])[C:14]([C:15]#[C:16][CH2:17][CH2:18][CH2:19][N:20]3[C:21](=[O:30])[C:22]4[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:28]3=[O:29])=[CH:13][N:12]=2)[CH:37]=[CH:36][CH:35]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCC#Cc1cnc(Nc2cccc(F)c2)nc1OCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: O=C1c2ccccc2C(=O)N1CCCC#Cc1cnc(Nc2cccc(F)c2)nc1O
Reaction time: 8 h
Yield: 109.3 %

Procedure:
To 2-(5-(4-(benzyloxy)-2-((3-fluorophenyl)amino)pyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J3, 69 mg), trifluoroacetic acid (1 mL) was added at room temperature, and the mixture was stirred overnight at the same temperature. The solvent was evaporated under reduced pressure, and then ethyl acetate and water were added to the mixture. The organic layer was separated, washed with saturated aqueous sodium chloride, and then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid matter was washed with diisopropyl ether, and then dried under reduced pressure to obtain 2-(5-(2-((3-fluorophenyl)amino)-4-hydroxypyrimidin-5-yl)-4-pentyn-1-yl)isoindoline-1,3-dione (J4, 62 mg) as pale pink solid.
Reaction SMILES: [C:1]([O:4][C@H:5]([C@H:13]1[O:18][CH2:17][CH2:16][N:15]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[CH2:24][N:23]([CH3:28])[C:22]3=[O:29])[C:14]1=[O:30])[C:6]([O:8]C(C)(C)C)=[O:7])(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([O:4][C@H:5]([C@H:13]1[O:18][CH2:17][CH2:16][N:15]([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[CH2:24][N:23]([CH3:28])[C:22]3=[O:29])[C:14]1=[O:30])[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@@H](C(=O)OC(C)(C)C)[C@H]1OCCN(c2ccc3c(c2)C(=O)N(C)C3)C1=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)O[C@@H](C(=O)O)[C@H]1OCCN(c2ccc3c(c2)C(=O)N(C)C3)C1=O
Reaction time: 1 h
Yield: 88.3 %

Procedure:
To a solution of compound 70-3 (85 mg) in CH2Cl2 (2.5 mL) at 0° C. was added TFA (0.5 mL) dropwise. The mixture was stirred for 1 h at 0° C. and at rt for 30 min whereupon an additional portion of TFA (0.5 mL) was added. After an additional 1 h at rt, the mixture was diluted with CH2Cl2 and concentrated to dryness under reduced pressure. The crude mixture was redissolved in CH2Cl2 and concentrated and this protocol was repeated 5 times with to afford compound 70-4 (65 mg) as a light semisolid. LC-MS: M+H=363. This material was used without further purification.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.[CH3:9][C:10]1[N:15]=[C:14]([N:16]2[CH2:21][CH2:20][C:19](=[CH2:22])[CH2:18][CH2:17]2)[C:13]([N+:23]([O-:25])=[O:24])=[CH:12][CH:11]=1>>[CH3:9][C:10]1[N:15]=[C:14]([N:16]2[CH2:21][CH2:20][C:19]3([O:24][N:23]=[C:13]([C:12]#[C:8][C:4]4[CH:5]=[CH:6][CH:7]=[CH:2][N:3]=4)[CH2:22]3)[CH2:18][CH2:17]2)[C:13]([N+:23]([O-:25])=[O:24])=[CH:12][CH:11]=1
Reactant: Cc1cccc(Br)n1
Reactant: C=C1CCN(c2nc(C)ccc2[N+](=O)[O-])CC1
Product: Cc1ccc([N+](=O)[O-])c(N2CCC3(CC2)CC(C#Cc2ccccn2)=NO3)n1
Yield: 49.6 %

Procedure:
The title product was prepared replacing 2-iodopyridine for 2-bromo-6-methylpyridine following the procedure reported above for the compound of Example 3. Purification of the residue by automated flash liquid chromatography (Horizon®TM-Biotage) (Petroleum Ether-EtOAc gradient from 9:1 to 4:6). Yield: 49.6%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1I.[CH3:12][Si:13]([C:16]#[CH:17])([CH3:15])[CH3:14].C(N(CC)CC)C>CN(C=O)C.[Cu]I>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:17]#[C:16][Si:13]([CH3:15])([CH3:14])[CH3:12]
Reactant: C#C[Si](C)(C)C
Reactant: COC(=O)c1ccccc1I
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccccc1C#C[Si](C)(C)C
Temperature: 80 °C
Reaction time: 3 h
Yield: 85.1 %

Procedure:
To a solution of 2-iodo-benzoic acid methyl ester (792 mg, 3.02 mmol) in DMF (10 mL) are added trimethylsilylacetylene (854 μL, 6.04 mmol) and triethylamine (2.95 mL, 21.1 mmol). The reaction mixture is degassed for 20 minutes with a stream of nitrogen. Dichloro(bistriphenylphosphene) palladium (II) (212 mg, 0.302 mmol, 10 mol %) and copper (I) iodide (58 mg, 0.302 mmol, 10 mol %) are added and the reaction is heated to 80° C. After 3 h, the reaction is concentrated and the residue is chromatographed eluting with 0 to 5% EtOAc/Hexanes to yield the title compound (597 mg, 85%). GC/MS: 232.
Reaction SMILES: [C:1]([O:5][C:6](=[O:24])[NH:7][C:8]1[CH:13]=[C:12]([NH:14][CH2:15][CH:16]([CH3:18])[CH3:17])[C:11]([C:19]([F:22])([F:21])[F:20])=[CH:10][C:9]=1[NH2:23])([CH3:4])([CH3:3])[CH3:2].C([O:29][C:30](=O)[CH2:31][C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([N:40]2[CH:44]=[CH:43][N:42]=[CH:41]2)[CH:35]=1)=[O:33])(C)(C)C>>[C:1]([O:5][C:6](=[O:24])[NH:7][C:8]1[CH:13]=[C:12]([NH:14][CH2:15][CH:16]([CH3:17])[CH3:18])[C:11]([C:19]([F:22])([F:21])[F:20])=[CH:10][C:9]=1[NH:23][C:30](=[O:29])[CH2:31][C:32]([C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([N:40]2[CH:44]=[CH:43][N:42]=[CH:41]2)[CH:35]=1)=[O:33])([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2ccnc2)c1
Reactant: CC(C)CNc1cc(NC(=O)OC(C)(C)C)c(N)cc1C(F)(F)F
Product: CC(C)CNc1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3ccnc3)c2)cc1C(F)(F)F

Procedure:
The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg, 1.0 mmol) and 3-(3-imidazol-1-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 77%).
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH:2]=[CH2:3].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.Br[C:37]1[CH:38]=[CH:39][C:40]2[C:41]3[N:50]([CH2:51][CH:52]([CH3:54])[CH3:53])[C:49]([CH2:55][CH2:56][CH2:57][CH3:58])=[N:48][C:42]=3[C:43]([NH2:47])=[N:44][C:45]=2[CH:46]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[NH2:47][C:43]1[C:42]2[N:48]=[C:49]([CH2:55][CH2:56][CH2:57][CH3:58])[N:50]([CH2:51][CH:52]([CH3:53])[CH3:54])[C:41]=2[C:40]2[CH:39]=[CH:38][C:37](/[CH:3]=[CH:2]/[C:1]([O:5][CH3:6])=[O:4])=[CH:46][C:45]=2[N:44]=1
Reactant: CCCCc1nc2c(N)nc3cc(Br)ccc3c2n1CC(C)C
Reactant: C=CC(=O)OC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCCc1nc2c(N)nc3cc(/C=C/C(=O)OC)ccc3c2n1CC(C)C
Temperature: 100 °C
Yield: 72.3 %

Procedure:
A thick walled glass tube, equipped with stir bar, was charged with palladium (II) acetate (18 mg, 0.08 mmol), acetonitrile (2 mL), methyl acrylate (69 mg, 0.8 mmol), triethylamine (240 mg, 2.4 mmol), tri-o-tolylphosphine (49 mg, 0.16 mmol) and 7-bromo-2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (U.S. Patent Application Publication No. US 2004/0147543 Example 1, 300 mg, 0.8 mmol). The reaction mixture was purged with nitrogen and the tube was sealed and heated to 100° C. in an oil bath. The mixture became an amber homogeneous solution after approximately 5 minutes. The reaction was maintained at 100° C. for 32 hours and then concentrated to dryness. The reaction mixture was taken up in water and dichloromethane. Saturated aqueous potassium carbonate solution was added, adjusting to pH 11. The organic layer was separated and concentrated to a golden syrup. The crude product was purified by flash chromatography on silica gel (eluting with 5% methanol/dichloromethane). The resulting tan solid (230 mg) was recrystallized from acetonitrile to give 220 mg of Methyl(2E)-3-[4-amino-2-butyl-1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]prop-2-enoate as a pale gold solid, mp 193-194° C.
Reaction SMILES: C(OC([NH:8][N:9]([C:13]([C:15]1[S:16][C:17]2[CH2:18][CH2:19][O:20][C:21]3[CH:28]=[C:27]([Br:29])[CH:26]=[CH:25][C:22]=3[C:23]=2[N:24]=1)=[O:14])[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.[ClH:30].O1CCOCC1>CO>[ClH:30].[CH:10]([N:9]([C:13]([C:15]1[S:16][C:17]2[CH2:18][CH2:19][O:20][C:21]3[CH:28]=[C:27]([Br:29])[CH:26]=[CH:25][C:22]=3[C:23]=2[N:24]=1)=[O:14])[NH2:8])([CH3:12])[CH3:11]
Reactant: CC(C)N(NC(=O)OC(C)(C)C)C(=O)c1nc2c(s1)CCOc1cc(Br)ccc1-2
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: CC(C)N(N)C(=O)c1nc2c(s1)CCOc1cc(Br)ccc1-2
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 96 %

Procedure:
A suspension of N′-(8-bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbonyl)-N′-isopropyl-hydrazinecarboxylic acid tert-butyl ester (6.14 g, 12.7 mmol) in methanol (49 mL) was treated with 4N HCl in dioxan (12.7 mL, 51.0 mmol) and stirred at RT for 0.75 h before being warmed to 50° C. and stirred for 3 h. The reaction mixture was concentrated in vacuo and the resultant solid was triturated with diethyl ether to give the title compound as a yellow brown solid (5.14 g, 12.3 mmol, 96%). LCMS: RT=4.79 min, [M+H]+=382/384.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH3:17])[CH3:15])[C:11]([CH3:18])=[CH:10][C:9]=1[NH:19][C:20](=[O:36])[CH2:21][C:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[O:34][N:33]=[C:32]([CH3:35])[CH:31]=2)[CH:25]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:16]([N:14]([CH3:15])[C:12]1[C:11]([CH3:18])=[CH:10][C:9]2[NH:19][C:20](=[O:36])[CH2:21][C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:30]4[O:34][N:33]=[C:32]([CH3:35])[CH:31]=4)[CH:25]=3)=[N:7][C:8]=2[CH:13]=1)[CH3:17]
Reactant: CCN(C)c1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-c3cc(C)no3)c2)cc1C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCN(C)c1cc2c(cc1C)NC(=O)CC(c1cccc(-c3cc(C)no3)c1)=N2

Procedure:
The title compound was prepared from (5-(ethyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M86) (0.38 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (160 mg, 55%).
Reaction SMILES: C([O:3][C:4](=[O:28])[CH2:5][S:6][C:7]1[S:11][C:10]([NH:12][C:13]([N:15]([CH:21]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:14])=[N:9][CH:8]=1)C.C1(NC2CCCC2)CCCCCC1.NC1SC=NC=1.C(OC(=O)CS)C>>[CH:21]1([N:15]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13](=[O:14])[NH:12][C:10]2[S:11][C:7]([S:6][CH2:5][C:4]([OH:28])=[O:3])=[CH:8][N:9]=2)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]1
Reactant: CCOC(=O)CSc1cnc(NC(=O)N(C2CCCCCC2)C2CCCC2)s1
Agent: C1CCCC(NC2CCCC2)CC1
Agent: CCOC(=O)CS
Agent: Nc1cncs1
Product: O=C(O)CSc1cnc(NC(=O)N(C2CCCCCC2)C2CCCC2)s1

Procedure:
[2-(3-Cycloheptyl-3-cyclopentyl-ureido)-thiazol-5-ylsulfanyl]-acetic acid ethyl ester prepared as described in general procedures (A) and (B) using cycloheptyl-cyclopentylamine and 5-aminothiazole-2-mercaptoacetic acid ethyl ester. Hydrolysis using general procedure (F) gave the title compound.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](Cl)=[O:9].ClC1C(C(F)(F)F)=C[N:15]=C2NC=C(N)C=12>N1C=CC=CC=1>[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([NH2:15])=[O:9]
Reactant: O=C(Cl)c1ccccn1
Reactant: Nc1c[nH]c2ncc(C(F)(F)F)c(Cl)c12
Agent: Cl
Solvent: c1ccncc1
Product: NC(=O)c1ccccn1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 224.8 %

Procedure:
Picolinoyl chloride hydrochloride (270 mg, 1.53 mmol) was added to 4-chloro-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-amine (240 mg, 1.02 mmol, Example 11, step G) in pyridine (5 mL). The reaction was stirred at 0° C. for 10 minutes, and then the pyridine was removed. THF (5 mL) and 2N LiOH (3 mL) were added and stirred for 20 minutes. The THF was removed, and water (20 mL) was added. The solid formed was collected by filtration and dried to give N-(4-chloro-5-(trifluoromethyl)-1H-pyrrolo[2, 3-1)]pyridin-3-yl)picolinamide (280 mg, 79% yield) as a solid.
Reaction SMILES: B(O)O.Br[C:5]1[N:10]=[C:9]([CH:11]=[O:12])[C:8]([F:13])=[CH:7][CH:6]=1.[S:14]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15]1>>[F:13][C:8]1[C:9]([CH:11]=[O:12])=[N:10][C:5]([C:16]2[CH:17]=[CH:18][S:14][CH:15]=2)=[CH:6][CH:7]=1
Reactant: OB(O)c1ccsc1
Reactant: O=Cc1nc(Br)ccc1F
Agent: OBO
Product: O=Cc1nc(-c2ccsc2)ccc1F

Procedure:
3-fluoro-6-(thiophen-3-yl)picolinaldehyde was prepared using the general boronic acid coupling procedure for 6-bromo-3-fluoropicolinaldehyde and thiophen-3-ylboronic acid (80.5 mg, 101.5 mg theoretical, 79.3%). LC-MS m/z 208.2 (M+1).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[O:11][CH2:12][CH2:13][CH2:14][O:15]CC2C=CC=CC=2)=[C:4]([O:23][CH2:24][CH3:25])[N:3]=1>[Pd].C(O)=O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[O:11][CH2:12][CH2:13][CH2:14][OH:15])=[C:4]([O:23][CH2:24][CH3:25])[N:3]=1
Reactant: CCOc1nc(N)nc2c1ncn2OCCCOCc1ccccc1
Agent: [Pd]
Solvent: O=CO
Product: CCOc1nc(N)nc2c1ncn2OCCCO
Temperature: 20 °C
Reaction time: 0.75 h
Yield: 56.1 %

Procedure:
A mixture of 2-amino-9-(3-benzyloxyprop-1-oxy)-6-ethoxypurine (350 mg, 1.02 mmol), 10% palladium on charcoal (350 mg) and 80% formic acid (10 ml) was stirred at 20° C. under an atmosphere of hydrogen for 45 minutes. The catalyst was removed and the solution was evaporated under reduced pressure. The residue was dissolved in water (10 ml) and heated to boiling. Concentrated aqueous ammonia (1 ml) was then added and the solution heated for 15 minutes and then cooled and evaporated under reduced pressure. Recrystallisation of the residue from water afforded the title compound (145 mg, 56%). IR: υmax (KBr) 3376, 3326, 3205, 1649, 1611, 1581, 1509, 1454, 1402 cm-1. 1H NMR: δH [(CD3)2SO] 1.35 (3H, dd, J=6.9, 7.1 Hz, CH2CH2O), 2.50 (2H, quintet, J=6.3, 6.6 Hz, CH2), 3.56 (2H, dt, J=5.2, 6.3 Hz, CH2OH), 4.35 (2H, t, J=6.6 Hz, CH 2 ON), 4.45 (2H, quartet, J=6.9, 7.1 Hz, OCH2CH3), 4.61 (1H, t, J=5.2 Hz, D2O exchangeable, OH), 6.56 (2H, br.s, D2O exchangeable, NH2), 8.09 (1H, s, H-8). Found: C, 47.16; H, 5.92; N, 27.60%. C10H15N5O3 requires: C, 47.41; H, 5.98; N, 27.65%.
Reaction SMILES: CC1C=CC(S([N:11]2[CH2:17][CH2:16][C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:13]3[CH:23]=[CH:24][CH:25]=[CH:26][C:12]2=3)(=O)=O)=CC=1.CS(O)(=O)=O.C1(SC)C=CC=CC=1.N>FC(F)(F)C(O)=O>[NH:11]1[CH2:17][CH2:16][C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:13]2[CH:23]=[CH:24][CH:25]=[CH:26][C:12]1=2
Reactant: CCOC(=O)C1=Cc2ccccc2N(S(=O)(=O)c2ccc(C)cc2)CC1
Agent: CS(=O)(=O)O
Agent: N
Solvent: CSc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)C1=Cc2ccccc2NCC1
Temperature: 0 °C
Reaction time: 3.5 h
Yield: 86.6 %

Procedure:
The ethyl 1-(4-methylphenylsulfonyl)-2,3-dihydro-1H-benz[b]azepine-4-carboxylate (0.63 g, 1.70 mmol) synthesized in Reference Example 4 was added to a mixture of trifluoroacetic acid (10 ml), methanesulfonic acid (0.30 g) and thioanisole (1.0 ml) which had been cooled to 0° C., and the resulting mixture was stirred at room temperature for 3.5 hours. The reaction mixture was poured into cooled aqueous ammonia and extracted twice with ethyl acetate, and the extract solution was washed twice with a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent; ethyl acetate:n-hexane=5:95) to obtain 0.32 g of ethyl 2,3-dihydro-1H-benz [b]azepine-4-carboxylate.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].C(OCC)C>>[CH3:3][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C@H:12]([C@H:13]3[C@H:23]([CH2:24][CH2:25]2)[C@:21]2([CH3:22])[C:16]([CH2:17][C@@H:18]([O:28][CH2:29][C:30]([OH:32])=[O:31])[CH2:19][CH2:20]2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:1]
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OCC(=O)OC(C)(C)C)CC[C@]4(C)[C@H]3CC[C@]12C
Solvent: CCOCC
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OCC(=O)O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 64 °C
Reaction time: 5 h
Yield: 101.2 %

Procedure:
To a solution of tert-Butyl cholest-5-en-3β-yloxyacetate (general formula XII, where n2=1; 111 mg, 0.22 mmol) in diethyl ether (8 ml) formic acid (5 ml, 132 mmol) was added and the solution was stirred at 64° C. for 5 h. The solvents were evaporated in vacuo and the residue was lyophilized from dioxane (20 ml) to afford Cholest-5-en-3β-yloxyacetic acid (general formula IX, where n2=1; 99 mg, 100%). 1H NMR (400 MHz, CDCl3) δ (ppm): 5.33-5.41 m, 1H (H-6); 4.16 s, 2H (H-1′); 3.31 tt, J=11.20, 4.60 Hz, 1H (H-3); 2.35-2.43 m, 1H (H-4a); 2.23-2.33 m, 1H (H-4b); 1.76-2.07 m, 5H (CH-1, H-12, H-2, H-7, H-16); 1.01 s, 3H (CH3-19); 0.92 d, J=6.57 Hz, 3H (CH3-21); 0.88 d, J=1.77 Hz, 3H (CH3-26); 0.86 d, J=1.64 Hz, 3H (CH3-27); 0.79-1.67 m, 33H (cholesteryl); 0.68 s, 3H (CH3-18); 13C NMR (101 MHz, CDCl3) δ (ppm): 172.98 (C-2′) 139.88 (C-5) 122.45 (C-6) 80.49 (C-1) 65.20 (C-1′) 56.72 (C-14) 56.15 (C-17) 50.10 (C-9) 42.31 (C-13) 39.73 (C-12) 39.51 (C-24) 38.69 (C-4) 36.96 (C-1) 36.76 (C-10) 36.18 (C-22) 35.78 (C-20) 31.91 (C-7) 31.85 (C-8) 28.21 (C-2) 28.10 (C-16) 28.01 (C-25) 24.27 (C-15) 23.82 (C-23) 22.81 (C-26) 22.55 (C-27) 21.06 (C-11) 19.32 (C-19) 18.71 (C-21) 11.86 (C-18); for C29H48O3 monoisotopic mass: calculated: 444.4. found: MS ESI m/z: 467.9 [M+Na]+. for C29H48O3—Na+ HR-MS calculated: 467.3496. found: 467.3496; IR (CHCl3): 3517, 1783, 1731, 1287 (COOH); 1133, 1110, 1087, 1070, 842 (ether); 1668, 1334 (C═C); 1381, 1367, 1170 (i-propyl); 2954, 2869, 1443, 1367 (Me); [α]D −16.1° (c 0.031; CHCl3).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=O)[NH:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].P(Cl)(Cl)(Cl)=O.C(N(CC)CC)C.[CH2:28]([NH2:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1>[CH2:28]([NH:35][C:6]1[C:5]2[C:10](=[CH:11][C:2]([Cl:1])=[C:3]([N+:13]([O-:15])=[O:14])[CH:4]=2)[N:9]=[CH:8][N:7]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: O=c1[nH]cnc2cc(Cl)c([N+](=O)[O-])cc12
Reactant: NCc1ccccc1
Solvent: CCN(CC)CC
Solvent: O=P(Cl)(Cl)Cl
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cc2c(NCc3ccccc3)ncnc2cc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.6 %

Procedure:
7-Chloro-6-nitro-4(3H)-quinazolone [J. Org. Chem., 40, 356 (1975) etc.] (10 g, 54.8 mmol) was added to phosphorus oxychloride (40 ml) under ice-cooling. A temperature of the mixture was gradually raised and the mixture was refluxed for 2 hours. After evaporation of the solvent under reduced pressure, a solution of triethylamine (200 ml, 1.43 mol) and benzylamine (40 ml, 366 mmol) dissolved in tetrahydrofuran (500 ml) was added to the residue under ice-cooling. A temperature of the mixture was raised to room temperature and the mixture was stirred overnight. After evaporation of the solvent under reduced pressure, water and chloroform were added and the organic layer was separated. The aqueous layer was extracted with chloroform and the chloroform layer was combined with the organic layer. The combined organic layer was washed with water and dried over anhydrous magnesium sulfate. After evaporation of the solvent under reduced pressure, a mixed solvent of methanol and water was added thereto. The precipitated crystals were filtered off to give the title compound (8.55 g, 49.6%).
Reaction SMILES: [NH2:1][C:2]1[O:6][N:5]=[C:4]([CH3:7])[C:3]=1[Br:8].[C:9]1([CH3:19])[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1>>[Br:8][C:3]1[C:4]([CH3:7])=[N:5][O:6][C:2]=1[NH:1][S:15]([C:12]1[CH:13]=[CH:14][C:9]([CH3:19])=[CH:10][CH:11]=1)(=[O:17])=[O:16]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Cc1noc(N)c1Br
Product: Cc1ccc(S(=O)(=O)Nc2onc(C)c2Br)cc1
Yield: 69 %

Procedure:
N-(4-Bromo-3-methyl-5-isoxazolyl)-4-toluenesulfonamide was prepared from 5-amino-4-bromo-3-methylisoxazole and 4-toluenesulfonyl chloride according to the procedures described in Example 40b. The crude product was purified by recrystallization from ethyl acetate/hexanes to give off-white crystals, m.p. 169°-172° C., yield 69%.