Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])[CH2:5][CH:6]=[CH2:7].I[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:28]2[N:33]=[CH:32][CH:31]=[CH:30][N:29]=2)=[CH:23][CH:22]=1>>[CH3:1][O:2][C:3](=[O:19])[CH:4]([NH:8][C:9](=[O:18])[C:10]1[C:11]([Cl:17])=[CH:12][CH:13]=[CH:14][C:15]=1[Cl:16])[CH2:5]/[CH:6]=[CH:7]/[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:34][CH:35]([CH3:37])[CH3:36])[C:28]2[N:29]=[CH:30][CH:31]=[CH:32][N:33]=2)=[CH:23][CH:22]=1
Reactant: CC(C)CN(c1ccc(I)cc1)c1ncccn1
Reactant: C=CCC(NC(=O)c1c(Cl)cccc1Cl)C(=O)OC
Product: COC(=O)C(C/C=C/c1ccc(N(CC(C)C)c2ncccn2)cc1)NC(=O)c1c(Cl)cccc1Cl
Yield: 63.8 %

Procedure:
In the same manner as in Example 1, 2-(2,6-dichlorobenzamido)pent-4-enoic acid methyl ester (143 mg) was reacted with N-(4-iodophenyl)-N-isobutylpyrimidin-2-amine (167 mg) to obtain (E)-2-(2,6-dichlorobenzamido)-5-[4-(isobutyl-pyrimidin-2-ylamino)phenyl]pent-4-enoic acid methyl ester (159 mg). Column chromatography (silica gel, eluent: hexane/ethyl acetate=1/1) was used for purification.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]3[N:25]=[CH:26][C:27]([C:28](O)=O)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].[OH:33][NH:34][C:35](=[NH:46])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([S:42](=[O:45])(=[O:44])[NH2:43])[CH:37]=1>>[F:32][C:2]([F:1])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[N:18]3[N:25]=[CH:26][C:27]([C:28]4[O:33][N:34]=[C:35]([C:36]5[CH:37]=[C:38]([S:42]([NH2:43])(=[O:44])=[O:45])[CH:39]=[CH:40][CH:41]=5)[N:46]=4)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:12])([F:13])[F:14]
Reactant: N=C(NO)c1cccc(S(N)(=O)=O)c1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(OCC(F)(F)F)c3)nc12
Product: NS(=O)(=O)c1cccc(-c2noc(-c3cnn4c(C(F)(F)F)cc(-c5ccc(C(F)(F)F)c(OCC(F)(F)F)c5)nc34)n2)c1

Procedure:
The title compound was prepared from 5-[3-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C. 10) (237 mg, 0.5 mmol) and N-hydroxy-3-sulfamoyl-benzamidine [CAS-No. 9000-88-7] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by flash chromatography (ethyl acetate/hexane) and crystallization (dichloromethane) as a light yellow solid (220 mg, 67%). MS (EI) 652.2 [(M)+]; mp 250° C.
Reaction SMILES: [Cl:1][C:2]1[S:6][N:5]=[C:4]([OH:7])[CH:3]=1.[C:8]1([CH:15]=CC(O)=[CH:11][CH:10]=1)[OH:9]>C1(C)C=CC=CC=1>[O:9]=[C:8]([CH3:15])[CH2:10][CH2:11][N:5]1[C:4](=[O:7])[CH:3]=[C:2]([Cl:1])[S:6]1
Reactant: Oc1ccc(O)cc1
Reactant: Oc1cc(Cl)sn1
Solvent: Cc1ccccc1
Product: CC(=O)CCn1sc(Cl)cc1=O

Procedure:
A solution of 5-chloro-3-hydroxyisothiazole (1.5 g, 0.011 mole), 2-trimethylysiloxy-1,3-butadiene (5.6 g, 0.04 mole) and 0.5 g of hydroquinone in 20 ml of toluene was heated at 80° C. for 96 hours. After cooling, the mixture was concentrated in vacuo. The residual oil was dissolved in diethyl ether and washed with saturated NaHCO3 solution and then with water. After drying (MgSO4) and concentrating the solution, the residual oil was purified by column chromatography on silica gel, using diethyl ether/methanol (9/1) as eluant. Compound 1 was obtained as an oil, 0.3 g; IR (neat) 1625, 1650 cm-1 ; NMR (CDCl3) δ6.25 (s, 1H); 4.0 (t, 2H); 2.9 (t, 2H); 2.2 (s, 3H).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([OH:14])[CH2:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[CH:8][CH:7]=1.[C:15](O[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])(OC(C)(C)C)=O.[Na+].[Cl-]>C1COCC1>[CH:6]([O:5][CH:4]([CH3:3])[CH3:15])([CH3:7])[CH3:13].[C:10]([C:9]1[CH:12]=[CH:13][C:6]([O:5][CH2:4][CH:3]([OH:14])[CH2:2][NH:1][C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[CH:7][CH:8]=1)#[N:11]
Reactant: N#Cc1ccc(OCC(O)CN)cc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCC(O)COc1ccc(C#N)cc1
Product: CC(C)OC(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A cooled (0° C.) solution of 4-[(3-amino-2-hydroxypropyl)oxy]benzonitrile (from step (ii) above; 44.6 g, 0.23 mol) in THF:H,O (1.5 L of 1:1) was treated with di-tert-butyl dicarbonate (53 g, 0.24 mol). The mixture was stirred at rt overnight, after which NaCl was added and the resulting organic layer separated. The water layer was extracted with ether and the combined organics were dried and concentrated in vacuo. The resulting oil (70 g) was filtered through a plug of silica, and then crystallised from diethyl ether:di-iso-propyl ether to yield 50 g of the sub-title compound.
Reaction SMILES: [C:1]1([C:7]2[CH:11]=[C:10]([NH:12][C:13](=[O:39])[O:14][CH2:15][C@@H:16]([N:25]([CH3:38])[C:26]([NH:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=3[Cl:37])=[O:27])[CH2:17][C@@H:18]3[CH2:22][O:21]C(C)(C)[O:19]3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1>CO>[C:1]1([C:7]2[CH:11]=[C:10]([NH:12][C:13](=[O:39])[O:14][CH2:15][C@@H:16]([N:25]([CH3:38])[C:26]([NH:28][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:31]=3[Cl:37])=[O:27])[CH2:17][C@@H:18]([OH:19])[CH2:22][OH:21])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CN(C(=O)NCc1cccc(F)c1Cl)[C@H](COC(=O)Nc1cc(-c2ccccc2)no1)C[C@@H]1COC(C)(C)O1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: CN(C(=O)NCc1cccc(F)c1Cl)[C@H](COC(=O)Nc1cc(-c2ccccc2)no1)C[C@@H](O)CO
Temperature: 25 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
To a solution of (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-((R)-2,2-dimethyl-1,3-dioxolan-4-yl)propyl 3-phenylisoxazol-5-ylcarbamate (0.4 g, 0.7 mmol, 1.0 equiv.) in MeOH (5 mL) at 0° C., was added HCl/Dioxane (4 N, 3 mL). The mixture was warmed up to RT, stirred for 1 h, concentrated and purified on silica gel column using a mixture of DCM and MeOH to give (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4,5-dihydroxypentyl 3-phenylisoxazol-5-ylcarbamate (0.35 g, 96%, white solid). LRMS (M+H+) m/z 521.1.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[C:15]3[CH:16]=[CH:17][CH2:18][O:19][C:14]=3[C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=2)=[CH:4][N:3]=1.ClC1C=CC=C(C(OO)=[O:32])C=1>CN(C=O)C>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][C:10]2[C:15]3[CH:16]=[CH:17][CH2:18][O:19][C:14]=3[C:13]([O:20][CH3:21])=[C:12]([O:22][CH3:23])[CH:11]=2)=[CH:4][N+:3]=1[O-:32]
Reactant: COc1cc(Cc2cnc(N)nc2N)c2c(c1OC)OCC=C2
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CN(C)C=O
Product: COc1cc(Cc2c[n+]([O-])c(N)nc2N)c2c(c1OC)OCC=C2
Reaction time: 18 h

Procedure:
To a solution of 2,4-diamino-5-(7,8-dimethoxy-2H-1-benzopyran-5-ylmethyl)pyrimidine (0.993 g, 3.16 mmol) in DMF (80 mL) was added a solution of m-chloroperbenzoic acid (0.641 g, 3.16 mmol as 85%) in DMF (10 mL) dropwise over 30 min. After 18 hr, the solvent was evaporated and the residue chromatographed on silica gel eluted with 10-15% methanol-methylene chloride. Recovered starting material eluted first (0.40 g) followed by title compound as a white powder (0.47 g). Recrystallization from absolute ethanol gave white crystals, mp 233°-234° dec.; assignment of N-1 oxide based on 13C-NMR: C-4 shifts from 154.40 to 161.28 ppm on acidification. Anal. Calcd for C16H18N4O4 : C, 58.17; H, 5.49; N, 16.96. Found: C, 57.81; H, 6.11; N, 16.84.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][C:15]([CH2:21][CH3:22])([CH2:19][CH3:20])[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[C:29]1([NH2:36])[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH:34]=1.[C:37](O)(=O)[CH3:38]>>[CH2:19]([C:15]1([CH2:21][CH3:22])[O:16][CH2:17][CH2:18][N:13]([CH2:12][C:7]2[N:8]([CH3:11])[C:9]3[C:5]([N:6]=2)=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=[C:2]([N:35]2[C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=4[N:36]=[C:37]2[CH3:38])[N:10]=3)[CH2:14]1)[CH3:20]
Reactant: CCC1(CC)CN(Cc2nc3c(N4CCOCC4)nc(Cl)nc3n2C)CCO1
Reactant: Nc1ccccc1N
Reactant: CC(=O)O
Product: CCC1(CC)CN(Cc2nc3c(N4CCOCC4)nc(-n4c(C)nc5ccccc54)nc3n2C)CCO1

Procedure:
Following the procedures for 157 and General Procedure J, 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-2,2-diethylmorpholine and benzene-1,2-diamine were reacted, followed by condensation with acetic acid to give 191. LCMS m/z: 505.3 (MH+)
Reaction SMILES: [C:1]([Cl:4])(Cl)=[S:2].[CH2:5]([O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([Si](C)(C)C)[CH2:12][CH2:11]1)=[O:9])[CH3:6]>C(OCC)C>[CH2:5]([O:7][C:8]([N:10]1[CH2:11][CH2:12][N:13]([C:1]([Cl:4])=[S:2])[CH2:14][CH2:15]1)=[O:9])[CH3:6]
Reactant: CCOC(=O)N1CCN([Si](C)(C)C)CC1
Reactant: S=C(Cl)Cl
Solvent: CCOCC
Product: CCOC(=O)N1CCN(C(=S)Cl)CC1
Temperature: 25 °C

Procedure:
To a solution of 4.66 ml of 85% thiophosgene in 200 ml of ethyl ether, cooled to -76° is added, while stirring and under nitrogen, a solution of 7 g of 1-ethoxycarbonyl-4-trimethylsilylpiperazine in 35 ml of ethyl ether over a period of 20 minutes. The mixture is allowed to warm up to room temperature overnight. The suspension is filtered and the filtrate is evaporated to dryness. The residue is crystallized from methylene chloridehexane to give 4-ethoxycarbonyl-1-piperazinylthiocarbonyl chloride, m.p. 107°-111°.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[NH2:6])[CH3:2].[C:16](O)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CN1CCOCC1.O.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:15])[C@@H:5]([NH:6][C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=1)[CH3:2]
Reactant: O=C(O)c1ccccc1
Reactant: CCOC(=O)[C@@H](N)Cc1ccc(O)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Solvent: O
Product: CCOC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
L-Tyrosine ethyl ester (0.28 g, 1.35 mmol) was dissolved in DMF (9 mL). Benzoic acid (1 eq, 1.35 mmol, 0.17 g) was added, followed by N-methylmorpholine (3 eq, 4.06 mmol, 0.45 mL), 1-hydroxybenzotriazole hydrate (1.2 eq, 1.62 mmol, 0.22 g), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.2 eq, 1.62 mmol, 0.31 g). The yellow solution was allowed to stir at room temperature under nitrogen for three days. The DMF was then removed by rotary evaporation and the resulting residue partitioned between ethyl acetate and water. The organic portion was separated and washed 3×H2O and 1×aq. saturated NaHCO3. It was dried over MgSO4, filtered, and concentrated to an oil. Trituration with diethyl ether induced formation of a white powder (0.32 g, 76%). MS (ES+) m/e 314 [M+H]+, 627.
Reaction SMILES: [Br:1][CH2:2][C@H:3]([CH3:6])[CH2:4][OH:5].N1C=CN=C1.[C:12]([Si:16](Cl)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([CH3:15])([CH3:14])[CH3:13].[Cl-].[NH4+]>CN(C)C=O>[Br:1][CH2:2][C@H:3]([CH3:6])[CH2:4][O:5][Si:16]([C:12]([CH3:15])([CH3:14])[CH3:13])([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C[C@H](CO)CBr
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: C[C@@H](CBr)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To an N,N-dimethylformamide solution (50.0 ml) of (2R)-3-bromo-2-methyl-1-propanol (7.63 g) were added under ice cooling imidazole (7.13 g) and tert-butylchlorodiphenylsilane (14.8 ml), followed by stirring at room temperature for 5 hours. The reaction solution was poured into a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography to afford {[(2R)-3-bromo-2-methylpropyl]oxy}(tert-butyl)diphenylsilane (19.2 g).
Reaction SMILES: [H-].[Na+].O1C[CH2:6][CH2:5][CH2:4]1.[OH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:25]=[CH:24][C:23]([O:26][CH2:27][CH3:28])=[CH:22][N:21]=2)=[CH:16][CH:15]=1.C(Br)CC>O>[CH2:4]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[N:25]=[CH:24][C:23]([O:26][CH2:27][CH3:28])=[CH:22][N:21]=2)=[CH:18][CH:19]=1)[CH2:5][CH3:6]
Reactant: C1CCOC1
Reactant: CCOc1cnc(-c2ccc(CCCCCO)cc2)nc1
Agent: [H-]
Agent: [Na+]
Solvent: CCCBr
Solvent: O
Product: CCCOCCCCCc1ccc(-c2ncc(OCC)cn2)cc1
Reaction time: 5 h

Procedure:
A mixture of 1.2 g of sodium hydride (60-65 wt. %) and 150 ml of tetrahydrofuran was treated with 8.5 g of 2-[4-(5-hydroxy-1-pentyl)phenyl]-5-(ethoxy)pyrimidine while gassing with nitrogen, stirred for 5 hours, treated with 4 g of propyl bromide and subsequently stirred at room temperature overnight. The reaction mixture was treated with 500 ml of water and extracted three times with 50 ml of diethyl ether each time. The combined organic phases were washed twice with 500 ml of concentrated sodium chloride solution each time, dried over magnesium sulfate, filtered and subsequently concentrated. Chromato- graphy of the residue on silica gel with hexane/ethyl acetate (vol. 9:1) and recrystallization from ethyl alcohol gave 7.5 g of pure 2-[4-(5-[propyloxy]-1-pentyl)phenyl]-5-(ethoxy)pyrimidine.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH2:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: BrCc1ccccc1
Product: Brc1ccc2c(ccn2Cc2ccccc2)c1
Yield: 77.7 %

Procedure:
The title compound was prepared from 5-bromoindole (5.02 g, 25.6 mmol) and benzyl bromide (6.7 mL, 56 mmol), following the procedure described in Step 1 of Example 5. Purification by flash chromatography on Biotage apparatus using hexane as an eluant yielded 1-benzyl-5-bromo-1H-indole as a white solid (5.69 g, 78%), mp 93-95° C. Mass spectrum (+ESI, [M+H]+) m/z 286; 1HNMR (500 MHz, DMSO-d6): δ 7.7 (d, 1H, J=1.8 Hz), 7.55 (d, 1H, J=3.1 Hz), 7.4 (d, 1H, J=8.7 Hz), 7.15-7.30 (m, 6H), 6.45 (dd, 1H, J=3.2 Hz and 0.6 Hz), and 5.45 ppm (s, 2H).
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[CH2:5][NH:4]1.C(N(CC)CC)C.[C:23](=[S:25])=[S:24].[N+:26]([C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Cl)=[CH:31][CH:30]=1)([O-:28])=[O:27]>CO>[OH:1][CH2:2][CH:3]1[CH2:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[CH2:5][N:4]1[C:23]([S:25][CH2:33][C:32]1[CH:35]=[CH:36][C:29]([N+:26]([O-:28])=[O:27])=[CH:30][CH:31]=1)=[S:24]
Reactant: OCC1Cc2c([nH]c3ccccc23)CN1
Reactant: S=C=S
Reactant: O=[N+]([O-])c1ccc(CCl)cc1
Solvent: CCN(CC)CC
Solvent: CO
Product: O=[N+]([O-])c1ccc(CSC(=S)N2Cc3[nH]c4ccccc4c3CC2CO)cc1

Procedure:
In the same manner as described in Example 29 by using (3RS)-3-hydroxymethyl-1,2,3,4-tetrahydro-β-carboline (1.01 g), triethylamine (0.77 ml), CS2 (0.33 ml), 4-nitrobenzyl chloride (1.08 g) and 80% methanol (20 ml), there is prepared the title compound (1.47 g, 71%) as pale yellow needles, m.p. 193°-194° C. (recrystallized from aqueous methanol), NMR (DMSO-d6, δ): 4.79 (s, 2H, ##STR14## Mass m/e: 244 (M+ -- ##STR15##
Reaction SMILES: C[O:2][C:3](=[O:32])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([O:28][CH:29]([F:31])[F:30])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=1[Cl:27])[C:10]([CH2:17][CH3:18])=[N:11]2.CO.O.[OH-].[Na+]>C(O)(=O)C>[Cl:27][C:21]1[CH:22]=[C:23]([Cl:26])[CH:24]=[CH:25][C:20]=1[CH2:19][C:9]1[C:10]([CH2:17][CH3:18])=[N:11][C:12]2[C:7]([C:8]=1[O:28][CH:29]([F:30])[F:31])=[C:6]([O:5][CH2:4][C:3]([OH:32])=[O:2])[CH:15]=[CH:14][C:13]=2[F:16]
Reactant: CCc1nc2c(F)ccc(OCC(=O)OC)c2c(OC(F)F)c1Cc1ccc(Cl)cc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: CCc1nc2c(F)ccc(OCC(=O)O)c2c(OC(F)F)c1Cc1ccc(Cl)cc1Cl

Procedure:
A solution of [3-(2,4-dichlorobenzyl)-4-difluoromethoxy-2-ethyl-8-fluoroquinolin-5-yloxy]acetic acid methyl ester (0.17 g), methanol (6 mL), water (0.3 mL) and 5.0 M aqueous sodium hydroxide solution (0.15 mL) was stirred at room temperature for 1 hour. The pH of the solution was adjusted to 5 by the addition of glacial acetic acid and the solvent removed under reduced pressure. The residue was diluted with water and the solid collected by filtration. Purification by column chromatography on silica gel, eluting with a mixture of dichloromethane and methanol (1:0 to 3:1 by volume) gave title compound as a white solid, 0.030 g.
Reaction SMILES: C1([NH:5][C:6]2[C:7]3[CH:31]=[CH:30][NH:29][C:8]=3[N:9]=[C:10]([NH:12]C3C=CC(S(N4CCC(O)CC4)(=O)=O)=CC=3)[N:11]=2)CCC1.CS(CC1C=CC(N)=CC=1)(=O)=O>>[N:9]1[C:8]2[NH:29][CH:30]=[CH:31][C:7]=2[C:6]([NH2:5])=[N:11][C:10]=1[NH2:12]
Reactant: O=S(=O)(c1ccc(Nc2nc(NC3CCC3)c3cc[nH]c3n2)cc1)N1CCC(O)CC1
Agent: CS(=O)(=O)Cc1ccc(N)cc1
Product: Nc1nc(N)c2cc[nH]c2n1

Procedure:
According to the general procedure for synthesis of 1-(4-(4-(cyclobutylamino)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)phenylsulfonyl)piperidin-4-ol, 4-(methylsulfonylmethyl)aniline and 2-Chloro-N-cylclobutyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine gave N4-cyclobutyl-N2-(4-methylsulfonylmethyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2,4-diamine (MS calcd for C18H21N5O2S 371.5, found [MH] 372.1; UV 205.1, 273.6, 304.5 nm).
Reaction SMILES: [CH2:1]([Si@H:6]1[CH2:11][CH2:10][C@H:9]([CH2:12][CH2:13][CH:14]2[CH2:19][CH2:18][CH:17](Br)[CH2:16][CH2:15]2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5].[Mg].Br[C:23]1[CH:28]=[C:27]([F:29])[C:26]([C:30]2[CH:35]=[C:34]([F:36])[C:33]([O:37][CH:38]([F:40])[F:39])=[C:32]([F:41])[CH:31]=2)=[C:25]([F:42])[CH:24]=1>C1COCC1>[CH2:1]([Si@H:6]1[CH2:11][CH2:10][C@H:9]([CH2:12][CH2:13][C@H:14]2[CH2:19][CH2:18][C@H:17]([C:23]3[CH:24]=[C:25]([F:42])[C:26]([C:30]4[CH:31]=[C:32]([F:41])[C:33]([O:37][CH:38]([F:39])[F:40])=[C:34]([F:36])[CH:35]=4)=[C:27]([F:29])[CH:28]=3)[CH2:16][CH2:15]2)[CH2:8][CH2:7]1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CCCCC[Si@H]1CC[C@H](CCC2CCC(Br)CC2)CC1
Reactant: Fc1cc(-c2c(F)cc(Br)cc2F)cc(F)c1OC(F)F
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCCC[Si@H]1CC[C@H](CC[C@H]2CC[C@H](c3cc(F)c(-c4cc(F)c(OC(F)F)c(F)c4)c(F)c3)CC2)CC1

Procedure:
36.0 g (0.1 mol) of 4-(2-(trans-4-n-pentyl-4-silacyclohexyl)ethyl)cyclohexyl bromide was dripped into a mixture of 2.5 g (0.11 mol) of magnesium and 300 ml of THF to obtain a Grignard's reagent. This solution was then dripped into a 500 ml THF solution of 0.5 g of tetrakis triphenylphosphine palladium and 87.1 g (0.1 mol) of 4-bromo-2,6,3',5'-tetrafluoro-4'-difluoromethoxybiphenyl. After a conventional after treatment, 4-(trans-4-(2-(trans-4-n-pentyl-4-silacyclohexyl)ethyl)cyclohexyl)-2,6,3',5'-tetrafluoro-4'-difluoromethoxybiphenyl was obtained. The silacyclohexane rings of the product were a mixture of trans isomers and cis isomers. They were separated by means of chromatography to obtain 40.0 g (yield 70.1%) of the trans isomer.
Reaction SMILES: BrC[CH2:3][CH2:4][CH2:5][CH2:6][C@@H:7]1[CH2:24][C:23]2[CH:22]=[C:21]([OH:25])[CH:20]=[CH:19][C:18]=2[C@@H:17]2[C@@H:8]1[C@H:9]1[C@@:13]([CH2:15][C@@H:16]2[F:26])([CH3:14])[CH:12]([OH:27])[CH2:11][CH2:10]1.[F:28][C:29]([F:57])([C:35]([F:56])([F:55])[C:36]([F:54])([F:53])[C:37]([F:52])([F:51])[C:38]([F:50])([F:49])[C:39]([F:48])([F:47])[C:40]([F:46])([F:45])[C:41]([F:44])([F:43])[F:42])[CH2:30][CH2:31][CH2:32][NH:33][CH3:34].[Cl-].[Na+].[CH3:60]N1CCCC1=O>>[F:26][C@H:16]1[CH2:15][C@@:13]2([CH3:14])[C@@H:9]([CH2:10][CH2:11][C@@H:12]2[OH:27])[C@H:8]2[C@H:17]1[C:18]1[CH:19]=[CH:20][C:21]([OH:25])=[CH:22][C:23]=1[CH2:24][C@H:7]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:34][N:33]([CH2:32][CH2:31][CH2:30][C:29]([F:57])([F:28])[C:35]([F:55])([F:56])[C:36]([F:53])([F:54])[C:37]([F:51])([F:52])[C:38]([F:49])([F:50])[C:39]([F:47])([F:48])[C:40]([F:45])([F:46])[C:41]([F:44])([F:43])[F:42])[CH3:60]
Reactant: C[C@]12C[C@H](F)[C@@H]3c4ccc(O)cc4C[C@@H](CCCCCBr)[C@H]3[C@@H]1CCC2O
Reactant: CNCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: CN1CCCC1=O
Agent: [Cl-]
Agent: [Na+]
Product: CN(CCCCC[C@@H]1Cc2cc(O)ccc2[C@@H]2[C@@H]1[C@@H]1CC[C@H](O)[C@@]1(C)C[C@@H]2F)CCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
A solution of 466 mg of 7α-(5-bromopentyl)-11β-fluor-estra-1,3,5(10)-triene-3,17-diol in 10 ml of 1-methyl-2-pyrrolidinone is stirred with 1.47 g of (4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluor-undecyl)-methyl-amine for 3 hours at a bath temperature of 80° C. For working-up, the batch is added to saturated sodium chloride solution, extracted with ether, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with ethyl acetate/methanol. 524 mg of 11β-fluoro-7α-{5-[(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluor-undecyl)-methyl-amino]-pentyl}-estra-1,3,5(10)-triene-3,17β-diol is obtained as a foam, [α]D=+24° (c=0.5 in CHCl3).
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]#[N:8])=[CH:5][NH:4][N:3]=1.CN(C)[CH:11]=[CH:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=O>C(O)(=O)C>[C:15]1([C:13]2[N:3]3[N:4]=[CH:5][C:6]([C:7]#[N:8])=[C:2]3[N:1]=[CH:11][CH:12]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: N#Cc1c[nH]nc1N
Reactant: CN(C)C=CC(=O)c1ccccc1
Solvent: CC(=O)O
Product: N#Cc1cnn2c(-c3ccccc3)ccnc12

Procedure:
A reaction mixture comprising 4.32 g. of 3-aminopyrazole-4-carbonitrile, 7.0 g. of 3-dimethylaminoacrylophenone and 25 ml. of glacial acetic acid is refluxed for 7 hours. The mixture is evaporated and the residue is treated as described in Example 1, giving the desired product, m.p. 230°-232° C.
Reaction SMILES: [NH3:1].[CH2:2]([O:4][C:5]([C:7]1[C:8]2[S:16][CH:15]=[C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4[N:26]=[N:27][N:28]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=5)[N:29]=4)[CH:20]=3)[C:9]=2[C:10](Cl)=[N:11][CH:12]=1)=[O:6])[CH3:3]>CC(O)C>[CH2:2]([O:4][C:5]([C:7]1[C:8]2[S:16][CH:15]=[C:14]([CH2:17][O:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4[N:26]=[N:27][N:28]([CH2:30][C:31]5[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=5)[N:29]=4)[CH:20]=3)[C:9]=2[C:10]([NH2:1])=[N:11][CH:12]=1)=[O:6])[CH3:3]
Reactant: N
Reactant: CCOC(=O)c1cnc(Cl)c2c(COc3cccc(-c4nnn(Cc5ccc(OC)cc5)n4)c3)csc12
Solvent: CC(C)O
Product: CCOC(=O)c1cnc(N)c2c(COc3cccc(-c4nnn(Cc5ccc(OC)cc5)n4)c3)csc12
Temperature: 140 °C

Procedure:
Ammonia gas was bubbled into a solution of 4-chloro-3-{3-[2-(4-methoxy-benzyl)-2H-tetrazol-5-yl]-phenoxy-methyl}-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester (0.17 g, 0.32 mmol) (from Example 27 supra) in 2-propanol (15 mL) for 20 minutes. The mixture was heated in a microwave reactor at 140° C. for 2 hours. The reaction mixture was concentrated. The residue washed with hot methanol, filtered and dried to give 4-amino-3-{3-[2-(4-methoxy-benzyl)-2H-tetrazol-5-yl]-phenoxymethyl}-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester. (Yield 0.15 g, 94%).