Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[C:2]([O:23]CC)(=O)[CH2:3][CH2:4]/[CH:5]=[CH:6]/[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]/[CH2:15][CH2:16][C:17]([O:19]CC)=O.Cl[Si](C)(C)C.CO>C1(C)C=CC=CC=1>[OH:19][CH:17]1[C:2](=[O:23])[CH2:3][CH2:4][CH:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]=[CH:14][CH2:15][CH2:16]1
Reactant: CCOC(=O)CC/C=C/CCCCCC/C=C/CCC(=O)OCC
Agent: C[Si](C)(C)Cl
Agent: O=C1CC/C=C/CCCCCC/C=C/CCC1O
Agent: [Na]
Solvent: CO
Solvent: Cc1ccccc1
Product: O=C1CCC=CCCCCCCC=CCCC1O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a 2 L Morton flask a mixture of sodium (7.48 g, 0.34 mole) in toluene (600 ml) was heated to reflux and stirred vigorously for 1 hour. To this solution was added dropwise (very slowly) a mixture of diethyl hexadeca-4E,12E-diene-1,16-dioate (24.86 g, 0.073 mole) and chlorotrimethylsilane (41.7 ml, 0.33 mole) in toluene (100 ml) over 2 hours. The reaction was heated to reflux for an additional 4 hours, then cooled to room temperature and stirred for an additional 16 hours. To the reaction mixture was added methanol (˜100 ml), the mixture is stirred 1 hour, and then left to stand for 1 hour. The resulting bi-phasic mixture was separated and the top layer is washed with 10% aqueous hydrochloric acid. The aqueous wash was re-extracted with ether and the organic layers are combined. The bottom layer from the bi-phasic mixture described above was combined with the aqueous wash and extracted again with diethyl ether. All organic layers were combined, dried with magnesium sulfate, filtered and evaporated to give the 16-hydroxycyclohexadeca-4E,12E-dien-1-one (20.0 g, 93% yield) as a brown oil which can be used directly in the next step. If desired, the material can be purified via reduced pressure distillation (210-220° C./0.3 mm Hg). C16H26O2 (250.38 g/mole). bp. 210-220° C./0.3 mm Hg. HNMR (500 MHz, CDCl3): 1.20-1.80 (m, 10H), 1.90-2.09 (m, 4H), 2.10-2.30 (m, 4H) 2.35 (m, 2H), 2.50 (m, 2H), 4.10 (m, 1H), 5.40 (m, 4H) ppm. 13CNMR (125 MHz, CDCl3): 27.8, 27.9*, 28.1, 28.5*, 31.4, 31.5, 32.8, 37.9, 76.2, 127.6, 128.8, 132.6, 133.1, 214 ppm. IR (νmax(cm−1)): 3450(b), 2940(s), 2910(s), 2850(s), 1720(s), 1440(m), 970(s). MS(m/z): 250(M+), 232, 221, 203, 189, 176, 161, 149, 135, 121, 109, 95, 81, 67, 55, 41.
Reaction SMILES: [CH3:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[C:16]3[C:11](=[CH:12][C:13]([C:17](O)=[O:18])=[CH:14][CH:15]=3)[O:10][C:9](=[O:20])[CH:8]=2)[N:6]=1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[OH:18][CH2:17][C:13]1[CH:12]=[C:11]2[C:16]([C:7]([C:5]3[N:6]=[C:2]([CH3:1])[S:3][CH:4]=3)=[CH:8][C:9](=[O:20])[O:10]2)=[CH:15][CH:14]=1
Reactant: Cc1nc(-c2cc(=O)oc3cc(C(=O)O)ccc23)cs1
Agent: CC(C)COC(=O)Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: C1CCOC1
Product: Cc1nc(-c2cc(=O)oc3cc(CO)ccc23)cs1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 4-(2-methyl-1,3-thiazol-4-yl)-2-oxo-2H-chromene-7-carboxylic acid (0.692 g, 2.41 mmol) in THF (16 ml) at 0° C. was added triethylamine (1.3 ml, 9.63 mmol) followed by isobutyl chloroformate (0.94 ml, 7.23 mmol) over 15 min. The reaction mixture was stirred at 0° C. for 1 h and sodium borohydride (0.456 g, 12.0 mmol) in water (12 ml) was added. The reaction mixture was stirred 1 h at 0° C., quenched with a solution of NH4Cl and extracted with EtOAc. The organic phase was washed with brine, dried over MgSO4 and evaporated to dryness. The residue was purified by chromatography on silica gel (hexanes-EtOAc, 4:6 to 2:8) to give the title compound. 1H NMR (400 MHz, acetone-d6): δ 8.22 (m, 1H), 8.05 (s, 1H), 7.40 (s, 1H), 7.35 (m, 1H), 6.62 (s, 1H), 4.80 (m, 2H), 4.55 (m, 1H), 2.82 (s, 3H).
Reaction SMILES: C[Mg]Br.[NH2:4][C:5]1[C:10]2=[CH:11][C:12]([CH:14]=[O:15])=[CH:13][N:9]2[N:8]=[CH:7][N:6]=1.[CH3:16]O.[NH4+].[Cl-]>C(OCC)C.C1COCC1.CCOC(C)=O>[NH2:4][C:5]1[C:10]2=[CH:11][C:12]([CH:14]([OH:15])[CH3:16])=[CH:13][N:9]2[N:8]=[CH:7][N:6]=1
Reactant: Nc1ncnn2cc(C=O)cc12
Reactant: CO
Agent: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(O)c1cc2c(N)ncnn2c1
Temperature: 25 °C
Yield: 56 %

Procedure:
To a solution of THF (100 mL) was added 3.0 M methylmagnesium bromide in diethyl ether (14.0 mL, 41.9, mmol) cooled in an ice bath. Then 4-aminopyrrolo[2,1-f][1,2,4]triazine-6-carbaldehyde (0.68 g, 4.19 mmol) was added as a solution in THF (200 mL) via an addition funnel. The reaction was allowed to slowly warm to rt over the following 17 h. The reaction was carefully treated with MeOH (10 mL) followed by aq saturated NH4Cl (50 mL) and EtOAc (50 mL). The solution was transferred to a separatory funnel and the organic layer was isolated while the aqueous layer was back extracted with EtOAc (4×20 mL). The combined organic layers were collected, dried (MgSO4), filtered, and concentrated to dryness. The crude material was then purified by flash chromatography (85:15 v/v CH2Cl2-MeOH). The purified fractions were concentrated in vacuo and then dried under vacuum to afford 422 mg of the above compound (2.37 mmol, yield 56%). 1H-NMR (DMSO-d6) δ 7.72 (s, 1H), 7.59 (br s, 2H), 7.45 (dd, J=0.5 Hz, 1.7 Hz, 1H), 6.76 (dd, J=0.5 Hz, 1.7 Hz, 1H), 5.03 (d, J=4.7 Hz, 1H), 4.79 (m, 1H), 1.38 (d, J=6.5 Hz, 3H); MS [M+H]+=179.3; LCMS RT=1.04 min.
Reaction SMILES: CC1(C)[O:6][C:5](=[CH:7][C:8]([N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH:21]([CH3:23])[CH3:22])[O:11][CH3:12])=[O:9])[C:4](=O)[O:3]1.[CH3:26][S:27]([NH2:30])(=[O:29])=[O:28]>>[CH:21]([O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:10]([O:11][CH3:12])[C:8](=[O:9])[CH:7]=[C:5]([OH:6])[C:4]([NH:30][S:27]([CH3:26])(=[O:29])=[O:28])=[O:3])([CH3:23])[CH3:22]
Reactant: CS(N)(=O)=O
Reactant: CON(Cc1ccccc1OC(C)C)C(=O)C=C1OC(C)(C)OC1=O
Product: CON(Cc1ccccc1OC(C)C)C(=O)C=C(O)C(=O)NS(C)(=O)=O
Yield: 52.1 %

Procedure:
Reaction of 2-(2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(2-isopropoxy-benzyl)-N-methoxy-acetamide (0.234 g, 0.67 mmol) with methanesulfonamide (0.064 g, 0.67 mmol) as described in the preparation of compound 22 gave 0.135 g (53% yield) of the title amide as a light yellow solid. 1H NMR (400 MHz, DMSO) δ: mixture of rotamers: 1.25 and 1.30 (2×3H, 2 d, J=6 Hz, CH3), 2.86 and 2.88 (3H, 2 S, SO2CH3), 3.63 and 3.67 (3H, 2 s, OCH3), 4.62 (1H, m, CH), 4.76 (2H, s, NCH2), 6.19 and 6.23 (1H, 2 s, CH), 6.8-7.2 (4H, m, aromatics). HRMS (ESI/neg) calculated for C16H21N2O7S: [M−H]−: 385.106948; found: 385.106655.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.O.[NH2:18][NH2:19].O>CN1CCCC1=O>[NH:18]([C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1)[NH2:19]
Reactant: NN
Reactant: O=S(=O)(c1ccc(F)cc1)N1CCOCC1
Solvent: O
Solvent: CN1CCCC1=O
Product: NNc1ccc(S(=O)(=O)N2CCOCC2)cc1
Temperature: 100 °C
Reaction time: 2 h

Procedure:
5 g of 4-fluorobenzenesulfonic acid morpholide were dissolved in 15 ml of N-methylpyrrolidone and mixed with 2.5 g of hydrazine hydrate, and the mixture was heated at 100° C. for 1 hour. After cooling to room temperature, 75 ml of water were added and the mixture was stirred at room temperature. After 2 hours, the solid was filtered off with suction and recrystallized from isopropanol.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N+:9]([O-])=O.[CH:12]([Mg]Br)=[CH2:13].[Cl-].[NH4+].C(OCC)(=O)C>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[C:4]2[C:3]=1[NH:9][CH:13]=[CH:12]2
Reactant: Cc1ccc(Br)c([N+](=O)[O-])c1
Reactant: C=C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1ccc(Br)c2[nH]ccc12
Reaction time: 1 h
Yield: 56.1 %

Procedure:
To 300 ml of a solution of 65.0 g (301 mmol) of 2-bromo-5-methylnitrobenzene in tetrahydrofuran was added 1 liter of a 1.0M solution of vinyl magnesium bromide (1 mol) in tetrahydrofuran at −60° C. in a nitrogen atmosphere under stirring during 1 hour. To the reaction mixed solution were added a saturated aqueous solution of ammonium chloride and ethyl acetate, and the resulting insoluble matters were filtered off. The resulting filtrate was dried over magnesium sulfate, concentrated, and then the resulting residue was purified by a silica gel column chromatography to give 35.5 g of the title compound.
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[C:3]1[CH:11]=[C:10]([CH:12]([OH:14])[CH3:13])[C:9]2[C:5](=[CH:6][N:7]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:8]=2)[CH:4]=1.[Cl:25][C:26]([Cl:30])([Cl:29])[C:27]#[N:28].N12CCCN=C1CCCCC2>ClCCl>[Cl:25][C:26]([Cl:30])([Cl:29])[C:27](=[NH:28])[O:14][CH:12]([C:10]1[C:9]2[C:5](=[CH:6][N:7]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:20])([CH3:22])[CH3:21])[N:8]=2)[CH:4]=[C:3]([C:2]([F:1])([F:23])[F:24])[CH:11]=1)[CH3:13]
Reactant: CC(O)c1cc(C(F)(F)F)cc2cn(COCC[Si](C)(C)C)nc12
Reactant: N#CC(Cl)(Cl)Cl
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Product: CC(OC(=N)C(Cl)(Cl)Cl)c1cc(C(F)(F)F)cc2cn(COCC[Si](C)(C)C)nc12
Reaction time: 4 h

Procedure:
To a solution of (±)-1-(5-(trifluoromethyl)-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-7-yl)ethanol (2.5 g, 6.94 mmol) and trichloroacetonitrile (6.95 mL, 69.4 mmol) in dichloromethane (50 mL) at room temperature was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.1 mL, 0.66 mmol). After stirring for 4 h, the reaction was concentrated and purified by column chromatography (12% EtOAc/Hex+0.1% Et3N) to give 3.1 g, (89%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.95 (s, 1H), 7.57 (s, 1H), 6.67 (q, J=6.6 Hz, 1H), 5.73 (s, 2H), 3.65 (t, J=8.4 Hz, 2H), 1.80 (d, J=6.6 Hz, 3H), 0.93 (m, 2H), −0.05 (s, 9H). Mass spec.: 526.90 (MH)+.
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:7]=[C:8]([C:12]2[CH:13]=[C:14]3[C:20]([C:21]4[CH:22]=[N:23][N:24]([CH2:26][C:27]5[CH:32]=[CH:31][CH:30]=[C:29]([N+:33]([O-:35])=[O:34])[CH:28]=5)[CH:25]=4)=[CH:19][N:18](C(OC(C)(C)C)=O)[C:15]3=[N:16][CH:17]=2)[CH:9]=[CH:10][CH:11]=1)(=[O:4])=[O:3].O1CCOCC1.Cl.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>CO.CCCCCC>[N+:33]([C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][CH:30]=1)[CH2:26][N:24]1[CH:25]=[C:21]([C:20]2[C:14]3[C:15](=[N:16][CH:17]=[C:12]([C:8]4[CH:7]=[C:6]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[CH:11]=[CH:10][CH:9]=4)[CH:13]=3)[NH:18][CH:19]=2)[CH:22]=[N:23]1)([O-:35])=[O:34]
Reactant: CC(C)(C)OC(=O)n1cc(-c2cnn(Cc3cccc([N+](=O)[O-])c3)c2)c2cc(-c3cccc(NS(C)(=O)=O)c3)cnc21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: CCCCCC
Product: CS(=O)(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cnn(Cc5cccc([N+](=O)[O-])c5)c4)c3c2)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 50 %

Procedure:
tert-butyl 5-(3-(methylsulfonamido)phenyl)-3-(1-(3-nitrobenzyl)-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (200 mg, 0.409 mmol) dissolved in 10 ml of methanol and added 1,4-dioxane/HCl (2 ml) at 0° C. and stirred at room temperature for 15 h. The reaction was monitored by TLC (30% ethyl acetate in hexane). The reaction mixture was concentrated under reduced pressure to afford crude product. The residue was basified with saturated sodium bicarbonate solution and extracted with ethyl acetate (2×25 ml). The organic layer was dried over Na2SO4, and concentrated under reduced pressure to afford 100 mg (62% yield) of the pure required product. 1H NMR (DMSO-d6, 400 MHz): δ11.82 (s, 1H), 9.85 (s, 1H), 8.47 (s, 2H), 8.33 (s, 1H), 8.18-8.15 (d, 2H), 8.00 (s, 1H), 7.806-7.7.800 (d, 1H), 7.75-7.34 (d, 1H), 7.69-7.65 (t, 1H), 7.52-7.44 (m, 3H), 7.24-7.22 (d, 1H), 5.55 (s, 2H), 3.05 (s, 3H). MS: m/z=489.3 (M+1), HPLC: 93.67% (method B).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17](F)[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:23][N:24]([CH3:28])[CH2:25][CH2:26][O-:27].[Na+].O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][N:16]=[C:17]([O:27][CH2:26][CH2:25][N:24]([CH3:28])[CH3:23])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:21]#[N:22])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: N#Cc1cnc2cnc(F)cc2c1Nc1ccc(F)c(Cl)c1
Reactant: CN(C)CC[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)CCOc1cc2c(Nc3ccc(F)c(Cl)c3)c(C#N)cnc2cn1
Yield: 66 %

Procedure:
To 250 mg of 4-(3-chloro-4-fluoro-phenylamino)-6-fluoro-[1,7]naphthyridine-3-carbonitrile under an inert atmosphere was added 8 mL of 1 M sodium (2-dimethylamino-ethoxide) in tetrahydrofuran. After refluxing for 2 hours, the reaction was stripped of tetrahydrofuran and water was added. The product was filtered, washed with water, dried, and recrystallized from chloroform/ether/hexanes to give 210 mg (66%) of 4-(3-chloro-4-fluoro-phenylamino)-6-(2-dimethylamino-ethoxy)-[1,7]naphthyridine-3-carbonitrile as a yellow solid: melting point 131-132° C.; mass spectrum (m/e): M+H 386.0.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=2I)[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2].[CH:26](/B(O)O)=[CH:27]\[CH3:28].C([O-])([O-])=O.[K+].[K+]>CCO.O1CCOCC1.[Pd]>[CH2:1]([O:3][C:4]([C:6]1([NH:15][C:16](=[O:25])[C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=2[CH:26]=[CH:27][CH3:28])[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7]1)=[O:5])[CH3:2]
Reactant: C/C=C/B(O)O
Reactant: CCOC(=O)C1(NC(=O)c2cccc(C)c2I)Cc2ccccc2C1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: C1COCCO1
Product: CC=Cc1c(C)cccc1C(=O)NC1(C(=O)OCC)Cc2ccccc2C1
Yield: 61.6 %

Procedure:
To a solution of 2-(2-iodo-3-methyl-benzoylamino)-indan-2-carboxylic acid ethyl ester (600 mg, 1.34 mmol) and trans-1-propen-1-ylboronic acid (460 mg, 5.36 mmol) in EtOH (10 mL) and dioxane (10 mL) is added palladium anchored homogeneous catalyst, FibreCatPd(0), (4.84% Pd, 285 mg, 0.13 mmol) and 2M aqueous solution of K2SO4 (2.68 mL, 5.36 mmol). The resulting reaction mixture is covered with argon and run in a microwave reaction: 110° C., 8 h. After concentration in vacuo, the residue is purified by HPLC and gave the pure product (142) as white solid (300 mg, 63%).
Reaction SMILES: [N:1]([C@H:4]1[C:7](=[O:8])[N:6]([Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[C@@H:5]1[C:16]([OH:18])=[O:17])=[N+:2]=[N-:3].CO.[CH2:21]1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[N:1]([C@H:4]1[C:7](=[O:8])[N:6]([Si:9]([C:12]([CH3:14])([CH3:15])[CH3:13])([CH3:11])[CH3:10])[C@@H:5]1[C:16]([O:18][CH3:21])=[O:17])=[N+:2]=[N-:3]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CC(C)(C)[Si](C)(C)N1C(=O)[C@H](N=[N+]=[N-])[C@H]1C(=O)O
Agent: CN(C)c1ccncc1
Solvent: CO
Solvent: ClCCl
Product: COC(=O)[C@@H]1[C@@H](N=[N+]=[N-])C(=O)N1[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of crude 131 (1.58 g) in CH2Cl2 (25 mL) was added methanol (0.26 mL, 6.43 mmol). DCC (1.45 g, 7.02 mmol) and catalytic DMAP. The solution was stirred at room temperature overnight. The solution was then filtered through Celite and concentrated in vacuo. The crude product was purified by silica gel column chromatography, eluting with 20% EtOAc in hexanes, to yield pure 132.
Reaction SMILES: [H-].[Na+].[OH:3]/[N:4]=[C:5](/[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:11]=1)\[C:6]([O:8]C)=[O:7].Cl[CH2:24][C:25]1[CH:44]=[CH:43][C:28]([O:29][CH2:30][C:31]2[N:32]=[C:33]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[O:34][C:35]=2[CH3:36])=[CH:27][CH:26]=1.Cl.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:36][C:35]1[O:34][C:33]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)=[N:32][C:31]=1[CH2:30][O:29][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][O:3]/[N:4]=[C:5](/[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=2)\[C:6]([OH:8])=[O:7])=[CH:44][CH:43]=1
Reactant: COC(=O)/C(=N\O)c1cccc(Oc2ccccc2)c1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc(CCl)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [H-]
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc(CO/N=C(\C(=O)O)c2cccc(Oc3ccccc3)c2)cc1
Reaction time: 1 h
Yield: 61.9 %

Procedure:
Sodium hydride (60% in oil, 107 mg) was added under a nitrogen atmosphere to a solution of methyl Z-2-hydroxyimino-2-(3-phenoxylphenyl)acetate (605 mg) and 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (700 mg) in N,N-dimethylformamide (10 ml) at room temperature and the mixture was stirred for 1 hour. After adding 1N HCl (5 ml), aqueous sodium bicarbonate was added, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel to obtain an oil from a fraction eluted with ethyl acetate-hexane (1:3, v/v). This oil was dissolved in tetrahydrofuran (10 ml)-methanol (5 ml), and 1N aqueous solution of sodium hydroxide (5 ml) was added and the mixture was stirred at 40° C. for 2 hours. 1N HCl (5.5 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residual crystal was recrystallized from ethyl acetate-hexane to obtain Z-2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]-2-(3-phenoxyphenyl)acetic acid (738 mg, yield 62%) as colorless crystals. m.p.: 173-174° C. (decomposition)
Reaction SMILES: [N+:1]([NH:4]C(OCC)=O)([O-:3])=[O:2].[NH4+:10].N>C(Cl)Cl>[NH2:4][N+:1]([O-:3])=[O:2].[NH2:4][N+:1]([O-:3])=[O:2].[NH4+:10]
Reactant: CCOC(=O)N[N+](=O)[O-]
Agent: N
Agent: [NH4+]
Solvent: ClCCl
Product: N[N+](=O)[O-]
Temperature: -50 °C
Reaction time: 1 h
Yield: 113.3 %

Procedure:
This solution was then added to a suspension of 7.5 grams (49.7 mmoles) of the ammonium N-nitrourethane prepared in Example I and suspended in 200 ml of methylene chloride which had been previously cooled to -50° C. before the addition. The reaction was allowed to proceed for one hour, warming to -30° C. over that hour. Excess ammonia gas was then added to raise the pH to 10. The solution was then filtered and the insoluble material was collected and digested 20 min in 150 ml of acetonitrile. The resulting suspension was filtered, and the filtrate was passed through a 4"×1" column of 230-400 mesh silica-gel, eluting with CH3CN. The filtrate was concentrated to 30 ml and treated with 30 ml CHCl3, resulting in the precipitation of 4.0 g of pure crystalline ammonium dinitramide mp 90-93° (60% yield).
Reaction SMILES: [C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].Cl.[NH2:8][CH2:9][CH2:10][N:11]1[C:19]2[C:18]([CH3:20])=[C:17]([CH3:21])[N:16]=[C:15]([NH2:22])[C:14]=2[N:13]=[C:12]1[CH3:23].NCCN1C2C(C)=C(C)N=C(N)C=2N=C1C.C(N(CC)CC)C>ClCCl>[NH2:22][C:15]1[C:14]2[N:13]=[C:12]([CH3:23])[N:11]([CH2:10][CH2:9][NH:8][C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])[C:19]=2[C:18]([CH3:20])=[C:17]([CH3:21])[N:16]=1
Reactant: Cc1nc(N)c2nc(C)n(CCN)c2c1C
Reactant: CC(C)C(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(N)c2nc(C)n(CCNC(=O)C(C)C)c2c1C
Reaction time: 0.25 h
Yield: 74.5 %

Procedure:
Isobutyryl chloride (1.3 mL, 12.2 mmol) was added dropwise to a mixture of 1-(2-aminoethyl)-2,6,7-trimethyl-1H-imidazo[4,5-c]pyridin-4-amine hydrochloride (4.0 g of material from Example 24, 12.2 mmol), triethylamine (85 mL, 610 mmol) and dichloromethane (400 mL). After 15 minutes analysis by high performance liquid chromatography indicated that the reaction was complete. The solvents were removed under reduced pressure. The residue was partitioned between chloroform (250 mL) and water (250 mL) containing 10 g of sodium carbonate (pH 12). This mixture was placed in a continuous extractor and extracted with chloroform for 24 hours. The extract was dried over magnesium sulfate and then concentrated under reduced pressure to provide a light yellow oil. The oil was purified by chromatography (silica gel eluting with 85/15 dichloromethane/methanol) to provide 2.63 g of N-[2-(4-amino-2,6,7-trimethyl-1H-imidazo[4,5-c]pyridin-1-yl)ethyl]-2-methylpropanamide as a white powder, m.p. 220-222° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].[C:10](=S)=[S:11].[OH-].[K+]>C(O)C>[Cl:8][C:6]1[CH:5]=[CH:4][C:3]2[O:9][C:10]([SH:11])=[N:1][C:2]=2[CH:7]=1
Reactant: S=C=S
Reactant: Nc1cc(Cl)ccc1O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: Sc1nc2cc(Cl)ccc2o1

Procedure:
A 2 g portion of 2-amino-4-chlorophenol was dissolved in 150 ml of ethanol, and the solution was mixed with 80 ml of carbon disulfide and 937 mg of potassium hydroxide and heated under reflux for 8 hours. The solvent was evaporated under a reduced pressure, and the residual oily mixture was mixed with 50 ml of 1 N hydrochloric acid aqueous solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate and then the solvent was evaporated under a reduced pressure. By recrystallizing the thus obtained mixture from ethyl acetate, the title compound (1.3 g) in light yellow color was obtained.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH:11]1[C:24]2[C:23]3([CH2:26][N:27]4[CH2:32][CH2:31][CH:30]([CH2:33][OH:34])[CH2:29][CH2:28]4)[CH2:25][CH:16]([C:17]4[C:22]3=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:15]=2[CH:14]=[CH:13][CH:12]=1.C(N(CC)CC)C.[OH-].[Na+]>ClCCl>[CH:21]1[C:22]2[C:23]3([CH2:26][N:27]4[CH2:32][CH2:31][CH:30]([CH:33]=[O:34])[CH2:29][CH2:28]4)[CH2:25][CH:16]([C:15]4[C:24]3=[CH:11][CH:12]=[CH:13][CH:14]=4)[C:17]=2[CH:18]=[CH:19][CH:20]=1
Reactant: OCC1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Agent: O=C(Cl)C(=O)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=CC1CCN(CC23CC(c4ccccc42)c2ccccc23)CC1
Temperature: -60 °C
Reaction time: 0.25 h
Yield: 79.3 %

Procedure:
A solution of oxalyl chloride (3.86 g, 30.4 mmol) in dichloromethane (100 mL) was cooled to -60° C. and treated dropwise with dimethylsulfoxide (2.49 g, 31.89 mmol), resulting in vigorous gas evolution. The resulting mixture was stirred at -60° C. for 15 min, then was treated dropwise with a solution of 1-(9,10-dihydro-9,10-methanoanthracen-9-ylmethyl)4- piperidinemethanol (6.47 g, 20.25 mmol) in dichloromethane (30 mL). This mixture was stirred at -60° C. for 1 h, then was treated with triethylamine (6.15 g, 60.75 mmol). The reaction was allowed to warm to room temperature, then was poured into 10% aqueous sodium hydroxide (50 mL) and extracted with chloroform (3×75 mL). The organic extracts were washed sequentially with 1N aqueous sodium hydroxide (50 mL) and brine (50 mL), combined, dried (K2CO3), filtered and evaporated to leave a tan solid. Trituration with hexane (50 mL) followed by filtration gave the title compound (5.09 g, 16.05 mmol, 79%) as a tan solid. 1H NMR (d6-DMSO): δ9.57 (s, 1H, CHO), 7.28 (m, 2H), 7.17 (m, 2H), 6.91 (m, 4H), 4.30 (s, 1H, H--C(10)), 3.34 (s, 2H, CH2N), 2.86 (m, 2H, eq-H--C(2')), 2.45 (s, 2H, H--C(11)), 2.29 (m, 3H, ax-H--C(2'), H--C(4')), 1.76 (m, 2H, eq-H--C(3')), 1.45 (m, 2H, ax-H--C(3')).
Reaction SMILES: I[CH:2]1[CH2:19][C@@:18]2([CH3:20])[C:5]([CH2:6][CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C:12]2=[O:21])=[CH:4][C:3]1=[O:22].C(=O)([O-])[O-].[Li+].[Li+].O>CN(C)C=O>[CH3:14][C@:13]12[CH2:15][CH2:16][C@H:17]3[C@@H:8]([CH2:7][CH2:6][C:5]4[C@:18]3([CH3:20])[CH:19]=[CH:2][C:3](=[O:22])[CH:4]=4)[C@@H:9]1[CH2:10][CH2:11][C:12]2=[O:21]
Reactant: C[C@]12CC(I)C(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: O=C([O-])[O-]
Agent: [Li+]
Solvent: O
Solvent: CN(C)C=O
Product: C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12

Procedure:
412 mg (1 mmol) of 2-iodo-androst-4-ene-3,17-dione of example 9 and 148 mg (2 mmol) of anhydrous lithium carbonate are stirred in 2 ml of dimethylformamide for 1 hour at 120° C. under nitrogen atmosphere. After cooling, it is added to water and extracted with ethyl acetate. The ethyl acetate solution is dried on sodium sulfate and then concentrated by evaporation. The residue is chromatographed on silica gel with ethyl acetate/hexane as mobile solvent. After concentration by evaporation of the fractions, 227 mg (80% of theory) of androsta-1,4-diene-3,17-dione of melting point 138°-139° C. is obtained.