Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:19][CH2:18][CH:14]([C:15](Cl)=[O:16])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]2[N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH:28]=[CH:29][C:22]=12.C(N(C(C)C)CC)(C)C>C(#N)C>[C:33]([O:32][C:30]([N:27]1[C:23]2=[N:24][CH:25]=[CH:26][C:21]([NH:20][C:15]([CH:14]3[CH2:18][CH2:19][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[O:10])[CH2:12][CH2:13]3)=[O:16])=[C:22]2[CH:29]=[CH:28]1)=[O:31])([CH3:36])([CH3:34])[CH3:35]
Reactant: O=C(Cl)C1CCN(C(=O)OCc2ccccc2)CC1
Reactant: CC(C)(C)OC(=O)n1ccc2c(N)ccnc21
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)n1ccc2c(NC(=O)C3CCN(C(=O)OCc4ccccc4)CC3)ccnc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 102.4 %

Procedure:
N-Benzyloxycarbonylisonipecotyl chloride (5 g) was added to a solution of 4-amino-1-tert-butoxycarbonyl-1H-pyrrolo[2,3-b]pyridine (3 g) and diisopropylethyamine (2.16 g) in acetonitrile (40 ml) and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice-water and extracted with chloroform. The residue obtained by water washing, drying and then concentration under reduced pressure was purified by silica gel column chromatography to give 6.3 g of N-(1-tert-butoxycarbonyl-1H-pyrrolo-[2,3-b]pyridin-4-yl)-1-benzyloxycarbonyl-4-piperidinecarboxamide.
Reaction SMILES: [CH2:1](N)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC([NH:19][C@H:20]([C:22]([NH:24][C@H:25]([P:27](=[O:30])([OH:29])[OH:28])C)=[O:23])[CH3:21])=O)C1C=CC=CC=1>CO>[NH2:19][C@H:20]([C:22]([NH:24][C@H:25]([P:27](=[O:28])([OH:30])[OH:29])[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:23])[CH3:21]
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C)P(=O)(O)O
Reactant: NCc1ccccc1
Solvent: CO
Product: C[C@H](N)C(=O)N[C@@H](Cc1ccccc1)P(=O)(O)O

Procedure:
In a manner analogous to that given in Example 1 (b) but with ion-exchange in methanol, from the benzylamine salt of (1R)-1-[(N-benzyloxycarbonyl-L-alanyl)amino]-ethylphosphonic acid there was obtained (1R)-1-(L-alanylamino)-2-phenylethylphosphonic acid of melting point 250°-260° C (decomposition); [α]D20 = -40.3° (c = 0.21% in water).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[NH:6][CH2:5]2.Br[C:13]1[C:21]2[CH2:20][CH2:19][CH:18]([NH2:22])[C:17]=2[CH:16]=[N:15][CH:14]=1.C([O-])([O-])=O.[Cs+].[Cs+].N[C@H]1CCCC[C@@H]1N>O1CCOCC1.[Cu]I.O>[NH2:22][CH:18]1[C:17]2[CH:16]=[N:15][CH:14]=[C:13]([N:6]3[CH2:5][C:4]4[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=4)[C:7]3=[O:11])[C:21]=2[CH2:20][CH2:19]1
Reactant: NC1CCc2c(Br)cncc21
Reactant: O=C1NCc2cc(Cl)ccc21
Agent: [Cu]I
Agent: N[C@H]1CCCC[C@@H]1N
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: NC1CCc2c1cncc2N1Cc2cc(Cl)ccc2C1=O
Temperature: 150 °C
Yield: 77.3 %

Procedure:
In a 25 mL sealed tube, 5-chloro-2,3-dihydro-isoindol-1-one (801 mg, 4.8 mmol), 4-bromo-6,7-dihydro-5H-[2]pyrindin-7-ylamine (intermediate B-18 [C], 937 mg, 4.4 mmol), CuI (200 mg, 1.1 mmol), Cs2CO3 (3.0 g, 9.2 mmol) and (+)-(S,S)-1,2-diaminocyclohexane (0.4 mL, 3.2 mmol) were dissolved in dioxane (16 mL). The resulting reaction mixture was heated at 150° C. for 3 hours before it was poured into H2O (50 mL) and extracted with EtOAc (2×125 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give a crude product which was purified by silica gel flash chromatography (30-100% EtOAc-hexane gradient) to yield the title compound (1.02 g, 80%) as a light yellow solid. MS: 300.2 (M+H+).
Reaction SMILES: [NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].[C:24]1([CH2:34][C@@H:35]([C:37]([OH:39])=[O:38])[NH2:36])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1.[NH2:40][C@H:41]([C:45]([O:47]CC=C)=[O:46])[CH:42]([CH3:44])[CH3:43].N1CCOCC1.[Sn]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4](=[O:10])[O:5][C:6]([CH3:9])([CH3:8])[CH3:7].[C:24]1([CH2:34][C@@H:35]([C:37]([OH:39])=[O:38])[NH2:36])[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][CH:25]=1.[NH2:40][C@H:41]([C:45]([OH:47])=[O:46])[CH:42]([CH3:44])[CH3:43]
Reactant: C=CCOC(=O)[C@@H](N)C(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)(C)OC(=O)C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: N[C@@H](Cc1cccc2ccccc12)C(=O)O
Solvent: C1COCCN1
Solvent: C1CCOC1
Product: CC(C)[C@H](N)C(=O)O
Reaction time: 72 h

Procedure:
Cbz-Asp(O-tBu)-3-(1-naphtyl)-L-alanine-Val-OAllyl (0.312 g, 0.47 mmol) was dissolved in THF (13 mL) and rotary evaporated to dryness, the sample was then redissolved in THF (13 mL) and vacuum aspirated (3*1 min of aspiration), followed by replacement of the atmosphere with Argon. Pd(PPh3)4 (0.060 g, 0.11 eq) was added in one shot, the flask was then evacued with Argon. Morpholine (0.267 mL, 4.42 eq) was added and the flask covered with a tin foil. The mixture was kept under stirring for 3 days under Argon. The sample was evaporated to dryness and the obtained residue was subjected to purification on C18 using a gradient of MeOH/solution of H2O at pH=3.5 (10 to 100%) to get 0.18 g of the desired compound.
Reaction SMILES: [Na].[CH3:2][C:3]([C:6]1[CH:21]=[CH:20][C:9]([C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[O:11])=[CH:8][CH:7]=1)([CH3:5])[CH3:4].Br[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25]>C(O)C>[CH3:5][C:3]([C:6]1[CH:21]=[CH:20][C:9]([C:10]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:17][CH:18]=2)=[O:11])=[CH:8][CH:7]=1)([CH3:2])[CH3:4]
Reactant: CC(C)(C)c1ccc(C(=O)Nc2ccc(O)cc2)cc1
Reactant: CCOC(=O)CBr
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)COc1ccc(NC(=O)c2ccc(C(C)(C)C)cc2)cc1

Procedure:
To a solution of 0.66 g. sodium in 25 ml. ethanol are added 7 g. 4-(1,1-dimethylethyl)-N-(4-hydroxyphenyl)benzamide (Example 2) and 3.2 ml. ethyl bromoacetate. The reaction mixture is boiled under reflux for 10 hours, the solvent is removed in a vacuum and the residue is recrystallised from toluene. There are obtained 5.5 g. (60% of theory) of the title compound; m.p. 119°-122° C.
Reaction SMILES: [BH4-].[Na+].C(O)C.C1COCC1.[Br:11][C:12]1[CH:13]=[C:14]([CH:17]=[C:18]([O:20][CH3:21])[CH:19]=1)[CH:15]=[O:16]>C(OCC)(=O)C>[Br:11][C:12]1[CH:13]=[C:14]([CH2:15][OH:16])[CH:17]=[C:18]([O:20][CH3:21])[CH:19]=1
Reactant: COc1cc(Br)cc(C=O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: C1CCOC1
Product: COc1cc(Br)cc(CO)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.3 %

Procedure:
NaBH4 (3.85 g; WAKO) was added to an ethanol (80 mL) and THF (20 mL) mixture solution of 3-bromo-5-methoxybenzaldehyde (22 g) with ice cooling and the resulting mixture was stirred at room temperature for 3 hours. The resulting mixture was poured into ice water (300 mL) and ethyl acetate (300 mL) was added thereto to extract the mixture with and the organic layer was washed with saturated aqueous sodium bicarbonate solution (300 mL) and then dried. The solvent was evaporated under reduced pressure to give the title compound (22.05 g).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]1[C@@H:12]([CH2:16][CH3:17])[C:13]([OH:15])=O.C(C1C=CC=CC=1C(O)=O)=O.C([O:33][C:34](=[O:52])[CH2:35][C@H:36]([NH2:51])[CH:37]([OH:50])[CH2:38][O:39][C:40]1[C:45]([F:46])=[C:44]([F:47])[CH:43]=[C:42]([F:48])[C:41]=1[F:49])(C)(C)C>>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]1[C@@H:12]([CH2:16][CH3:17])[C:13]([NH:51][C@H:36]([C:37](=[O:50])[CH2:38][O:39][C:40]1[C:45]([F:46])=[C:44]([F:47])[CH:43]=[C:42]([F:48])[C:41]=1[F:49])[CH2:35][C:34]([OH:52])=[O:33])=[O:15]
Reactant: CC[C@@H](C(=O)O)n1ccc2ccccc2c1=O
Reactant: CC(C)(C)OC(=O)C[C@H](N)C(O)COc1c(F)c(F)cc(F)c1F
Agent: O=Cc1ccccc1C(=O)O
Product: CC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)COc1c(F)c(F)cc(F)c1F)n1ccc2ccccc2c1=O

Procedure:
This compound was prepared using (S)-2-(1−oxo-1H-isoquinolin-2-yl)-butyric acid (prepared from 2-formylbenzoic acid using procedures similar to those described in methods A-E) and (3S)-3-amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester (prepared as described in methods N-P) using procedures similar to those described in methods F, G and E. The title compound was isolated by preparative HPLC. IR (solid) 2960.2, 1780.1, 1746.2, 1646.6, 1619.0, 1589.1, 1517.4, 1490.3, 1427.8, 1260.3, 1206.2, 1176.3, 1098.9, 938.4, 788.1, 748.3, 714.2, 692.5, 665.3 and 655.8 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 0.78-0.83 (3H, m), 1.89-1.96 (1H, m), 2.08-2.13 (1H, m), 2.50-2.78 (2H, m), 4.35-5.45 (4H, 3×m), 6.64-6.69 (1H, m), 7.74-7.73 (5H, m), 8.18-8.20 (1H, m), 8.81 & 8.90 (1H, d) ppm; 19F NMR (376 MHz, DMSO)(proton decoupled) δ −141.01, −141.03, −141.07, −141.09, −156.80, −156.82, −156.86, −156.88; MS ES (+) 509.2 (M+H).
Reaction SMILES: S(O[C@H:12]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C:14](=[CH:15][CH2:16][C@@H:17]3[C@@H:26]2[CH2:25][CH2:24][C@@:22]2([CH3:23])[C@H:18]3[CH2:19][CH2:20][C:21]2=[O:31])[CH2:13]1)(C1C=CC(C)=CC=1)(=O)=O.[CH3:32][OH:33]>>[CH3:32][O:33][C@H:12]1[CH2:29][CH2:28][C@@:27]2([CH3:30])[C:14](=[CH:15][CH2:16][C@@H:17]3[C@@H:26]2[CH2:25][CH2:24][C@@:22]2([CH3:23])[C@H:18]3[CH2:19][CH2:20][C:21]2=[O:31])[CH2:13]1
Reactant: Cc1ccc(S(=O)(=O)O[C@H]2CC[C@@]3(C)C(=CC[C@@H]4[C@@H]3CC[C@]3(C)C(=O)CC[C@@H]43)C2)cc1
Reactant: CO
Product: CO[C@H]1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C1

Procedure:
A solution of 3β-tosyloxyandrost-5-ene-17-one (18) (4.0 g. 9.05 mmol) in anhydrous methanol (120 mL) was refluxed for 2 h. The reaction mixture was concentrated under vacuum. On cooling, a white solid 3β-methoxyandrost-5-ene-17-one (19) was obtained. Recrystallization from methanol afforded shining crystals (2.57 g. 94%), m.p. 133-5° C. (lit m.p. 118-120° C. aq. MeOH).
Reaction SMILES: O.C(O)(C(F)(F)F)=O.[NH2:9][C:10]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:48]=[C:47]([Cl:49])[C:22]([CH2:23][C@@H:24]4[CH2:28][CH2:27][N:26]([N:29]5[CH2:34][CH2:33][CH:32]([O:35][Si](C(C)C)(C(C)C)C(C)C)[CH2:31][CH2:30]5)[C:25]4=[O:46])=[C:21]([Cl:50])[CH:20]=3)=[CH:18][C:13]=2[O:12][N:11]=1.C(OCC)(=O)C>C1COCC1>[NH2:9][C:10]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:48]=[C:47]([Cl:49])[C:22]([CH2:23][C@@H:24]4[CH2:28][CH2:27][N:26]([N:29]5[CH2:34][CH2:33][CH:32]([OH:35])[CH2:31][CH2:30]5)[C:25]4=[O:46])=[C:21]([Cl:50])[CH:20]=3)=[CH:18][C:13]=2[O:12][N:11]=1
Reactant: CC(C)[Si](OC1CCN(N2CC[C@@H](Cc3c(Cl)cc(-c4ccc5c(N)noc5c4)cc3Cl)C2=O)CC1)(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O=C(O)C(F)(F)F
Product: Nc1noc2cc(-c3cc(Cl)c(C[C@@H]4CCN(N5CCC(O)CC5)C4=O)c(Cl)c3)ccc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 86.7 %

Procedure:
Add water (3 mL) and TFA (1 mL) to (R)-3-[4-(3-amino-benzo[d]isoxazol-6-yl)-2,6-dichloro-benzyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one (0.095 g) in THF (3 mL). Stir the mixture at room temperature for 5 hours. Dilute the reaction with ethyl acetate, wash with sodium bicarbonate (sat. solution), separate the organic layer, dry over sodium sulfate, filter and concentrate. Purify the residue on silica gel column by using ethyl acetate first, then switch to 5% methanol in dichloromethane to afford 0.062 g (87%) of the desired product as white solid. MS (m/z): 475 (M+).
Reaction SMILES: [CH3:1][S:2]([NH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=O)(=[O:4])=[O:3].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(Cl)CCl>CN(C1C=CN=CC=1)C.C1COCC1>[C:15]1([NH:14][C:11](=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][NH:5][S:2]([CH3:1])(=[O:3])=[O:4])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CS(=O)(=O)NCCCCCC(=O)O
Reactant: Nc1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: C1CCOC1
Product: CS(=O)(=O)NCCCCCC(=O)Nc1ccccc1
Reaction time: 8 h
Yield: 95.8 %

Procedure:
To a solution of acid 69 (100 mg, 0.48 mmol), aniline (60 μL, 0.66 mmol), and DMAP (5 mg) in THF (5 mL) was added EDC (119 mg, 0.57 mmol). The reaction mixture was stirred overnight, then partitioned between H2O (10 mL) and EtOAc (15 mL). The layers were separated, and the aqueous portion extracted with EtOAc (3×10 mL). The organic fractions were combined, washed with sat. NH4Cl (5 mL), then brine, dried over MgSO4, and filtered. Concentration under reduced pressure gave 70 as a white crystalline solid (130 mg, 0.46 mmol, 95%). 1H-NMR (400 MHz, DMSO-d6) δ 9.84 (s, 1H), 7.57 (d, 2H), 7.26 (t, 2H), 7.00 (t, 1H), 6.92 (t, 1H), 2.91 (dt, 2H), 2.85 (s, 3H), 1.58 (m, 2H), 1.47 (m, 2H), 1.31 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:23]=[CH:22][C:5]([NH:6][C:7]2[CH:19]=[C:18]([CH:20]=[CH2:21])[CH:17]=[CH:16][C:8]=2[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][CH:3]=1.I[C:25]1[CH:34]=[CH:33][C:28]2[O:29][CH2:30][CH2:31][O:32][C:27]=2[CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[O:29]1[C:28]2[CH:33]=[CH:34][C:25](/[CH:21]=[CH:20]/[C:18]3[CH:17]=[CH:16][C:8]([C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10])=[C:7]([NH:6][C:5]4[CH:22]=[CH:23][C:2]([F:1])=[CH:3][CH:4]=4)[CH:19]=3)=[CH:26][C:27]=2[O:32][CH2:31][CH2:30]1
Reactant: Ic1ccc2c(c1)OCCO2
Reactant: C=Cc1ccc(C(=O)OC(C)(C)C)c(Nc2ccc(F)cc2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)c1ccc(/C=C/c2ccc3c(c2)OCCO3)cc1Nc1ccc(F)cc1
Temperature: 110 °C
Reaction time: 24 h

Procedure:
To toluene 3.0 mL solution of tert-butyl 2-(4-fluoroanilino)-4-vinylbenzoate 0.12 g were added 2,3-dihydro-6-iodobenzo[1,4]dioxin 0.20 g, cesium carbonate 0.25 g, tetrabutylammonium bromide 37 mg and polymer-carried bis(acetato)triphenylphosphine palladium(II) 58 mg at room temperature, and it was stirred at 110° C. for 24 hours. After the reaction mixture was cooled to room temperature, insoluble matter was filtrated, ethyl acetate and 10% citric acid aqueous solution were added to it. The organic layer was separated and collected, dried over anhydrous magnesium sulfate after sequential washing with 10% citric acid aqueous solution and saturated sodium chloride aqueous solution,the solvent was removed under reduced pressure. The obtained residue was refined by silica gel column chromatography [Trikonex company, Flash Tube 2008,eluent; hexane:ethyl acetate=4:1] to give tert-butyl 4-((E)-2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)vinyl)-2-(4-fluoroanilino)benzoate.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11](O)=[O:12])[CH:5]=[C:6]([F:8])[CH:7]=1.CO>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][OH:12])[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: O=C(O)CCc1cc(F)cc(F)c1
Solvent: CO
Solvent: C1CCOC1
Product: OCCCc1cc(F)cc(F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.6 %

Procedure:
Borane-tetrahydrofuran complex (0.095 mol) was added to a cooled (0°) solution of 3-(3,5-difluorophenyl)propanoic acid (0.043 mol) in tetrahydrofuran (75 ml). The reaction was stirred 2 hours at room temperature, then methanol was carefully added and the reaction was concentrated. The crude product was dissolved in ethyl ether, washed with water, dried over sodium sulfate and concentrated to yield 7 g (95%) of an oily product.
Reaction SMILES: [CH:1]([C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH2:15])=[NH:14])=[CH:11][CH:10]=1)=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[N+:18]([C:21]1[CH:32]=[CH:31][C:24]([CH:25]=[CH:26][S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([O-:20])=[O:19]>>[N+:18]([C:21]1[CH:22]=[CH:23][C:24]([CH:25]=[CH:26][S:27]([NH:14][C:13](=[NH:15])[C:12]2[CH:11]=[CH:10][C:9]([CH:1]=[CH:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[CH:17][CH:16]=2)(=[O:29])=[O:28])=[CH:31][CH:32]=1)([O-:20])=[O:19]
Reactant: O=[N+]([O-])c1ccc(C=CS(=O)(=O)Cl)cc1
Reactant: N=C(N)c1ccc(C=Cc2ccccc2)cc1
Product: N=C(NS(=O)(=O)C=Cc1ccc([N+](=O)[O-])cc1)c1ccc(C=Cc2ccccc2)cc1

Procedure:
Reaction of 4-styrylbenzamidine with 4-nitrostyrylsulfonyl chloride according to the procedure of Example 29 (a) provides N-(4-NITROSTYRYLSULFONYL)-4-STYRYLBENZAMIDINE.
Reaction SMILES: [C:1]([C:5]1[S:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11](Cl)=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH3:24][CH:25]1[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]1.O>CS(C)=O.C(Cl)(Cl)Cl>[C:1]([C:5]1[S:6][C:7]2[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[C:11]([N:27]3[CH2:28][CH2:29][CH2:30][CH:25]([CH3:24])[CH2:26]3)=[CH:10][C:8]=2[N:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC1CCCNC1
Reactant: CC(C)(C)c1nc2cc(Cl)c([N+](=O)[O-])cc2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Solvent: ClC(Cl)Cl
Product: CC1CCCN(c2cc3nc(C(C)(C)C)sc3cc2[N+](=O)[O-])C1

Procedure:
A solution of 2.7 g of 2-tert-butyl-5-chloro-6-nitrobenzothiazole described in example 5, in 25 ml of dimethyl sulfoxide is stirred and heated at 140° for 11 hours with 2.6 g of anhydrous potassium carbonate and 1 g of 3-methylpiperidine, cooled and poured into water. The material obtained is dissolved in chloroform and filtered through a silica gel column. The filtrate is evaporated to give 2-tert-butyl-5-[3-methylpiperidin-1-yl]-6-nitrobenzothiazole as an oil.
Reaction SMILES: [CH2:1]([N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[C:11]([O:18][CH3:19])[CH:10]=1)[CH2:4][CH3:5])[CH3:2]>C(O)C.[Pd]>[CH2:1]([N:3]([CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([O:18][CH3:19])[CH:10]=1)[CH2:4][CH3:5])[CH3:2]
Reactant: CCN(CC)CCOc1ccc([N+](=O)[O-])c(OC)c1
Agent: [Pd]
Solvent: CCO
Product: CCN(CC)CCOc1ccc(N)c(OC)c1

Procedure:
N,N-Diethyl-2-(3-methoxy-4-nitrophenoxy)ethylamine (140 mg, 0.5 mmol) was hydrogenated over Pd (5% on C, 50% wet, 40 mg) in ethanol (5 ml) for 16 hours. The catalyst was filtered off and the solvent removed under reduced pressure to afford the title compound as a brown oil. MS (m/z)=239 (M+H+); Calc'd for C13H22N2O2=238.33
Reaction SMILES: Br[C:2](Br)=[CH:3][C:4]1([CH3:8])[CH2:7][O:6][CH2:5]1.C([Li])CCC.[CH3:15][Si:16]([CH3:19])([CH3:18])Cl>C1COCC1.CCCCCC>[CH3:15][Si:16]([CH3:19])([CH3:18])[C:2]#[C:3][C:4]1([CH3:8])[CH2:7][O:6][CH2:5]1
Reactant: CC1(C=C(Br)Br)COC1
Reactant: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC1(C#C[Si](C)(C)C)COC1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 93.9 %

Procedure:
A 250-mL round-bottom flask was charged with 3-(2,2-dibromovinyl)-3-methyloxetane (2.177 g, 8.51 mmol) in THF (85 mL) to give a clear solution. The flask was cooled in a dry ice/acetone bath for 15 min, then n-butyllithium (7.83 mL, 19.56 mmol) (as a 2.5 M solution in hexane) was added dropwise over five min. After stirring at −78° C. for 45 min, trimethylchlorosilane (3.81 mL, 29.8 mmol) was added over 2 min. The cooling bath was removed after 30 min and the reaction was allowed to warm to RT for 30 min. The mixture was diluted with water (50 mL) and ether (50 mL). The layers were separated, and the aqueous layer was extracted with ether (25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and evaporated. The residue was dissolved in a small amount of ether and filtered through a small pad of silica gel. The filtrate was evaporated to give trimethyl((3-methyloxetan-3-yl)ethynyl)silane (1.344 g, 7.99 mmol, 94% yield) as a pale-yellow oil.
Reaction SMILES: [C:1]([N:4]([CH2:8][CH2:9][OH:10])[CH2:5][CH2:6][OH:7])(=[O:3])[CH3:2].C(N(CC)CC)C.Cl[C:19](Cl)([O:21]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[C:1]([N:4]1[CH2:8][CH2:9][O:10][C:19](=[O:21])[O:7][CH2:6][CH2:5]1)(=[O:3])[CH3:2]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CC(=O)N(CCO)CCO
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(=O)N1CCOC(=O)OCC1

Procedure:
The procedure of Example 1 was followed using N-acetyl diethanolamine (12.3 g, 83.9 mmol), triethylamine (24.0 mL, 167.8 mmol), dry THF (600 mL) and triphosgene (8.3 g, 28.8 mmol). The filtrate was concentrated yielding only oligomeric compounds.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8]([NH:9][C:10]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:7]([NH:29][CH:30]=[O:31])[CH:6]=[N:5]1.[H-].[Na+].Br[CH2:35][CH2:36][CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42].[I-].[Na+].S([O-])(O)(=O)=O.[K+]>CN(C)C=O>[CH:30]([N:29]([CH2:35][CH2:36][CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[C:7]1[CH:6]=[N:5][N:4]([CH2:3][CH2:2][OH:1])[C:8]=1[NH:9][C:10]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:31]
Reactant: CC(C)(C)OC(=O)NCCCBr
Reactant: O=CNc1cnn(CCO)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=S(=O)([O-])O
Agent: [H-]
Agent: [I-]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCN(C=O)c1cnn(CCO)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 36.2 %

Procedure:
To a stirred solution of [1-(2-hydroxyethyl)-5-(tritylamino)-1H-pyrazol-4-yl]formamide (2 g) in N,N-dimethylformamide (30 ml) was added sodium hydride (213 mg, 60% oil suspension) under a nitrogen stream at, 0° C., and the whole mixture was stirred at 0° C. for 20 minutes. A solution of tert-butyl (3-bromopropyl)carbamate (1.27 g) in N,N-dimethylformamide (10 ml) and sodium iodide (799 mg) were added to the above solution, and the mixture was stirred overnight. 10% Aqueous potassium hydrogen sulfate solution (5 ml) was added, and the whole mixture was extracted with ethyl acetate. The extract was washed with water and brine and dried over magnesium sulfate. Evaporation of the solvent under reduced pressure gave an oil, which was chromatographed on silica gel eluting with dichloromethane-ethyl acetate (2:1) to give tert-butyl (3-{N-formyl-N-[1-(2-hydroxyethyl)-5-(tritylamino)-1H-pyrazol-4-yl]amino}propyl)carbamate (1 g). The NMR spectrum of this compound indicates the existence of its rotamer.
Reaction SMILES: [BH4-].[Na+].[NH2:3][C:4]1[C:9]([C:10]#[N:11])=[CH:8][C:7]([C:12](=[O:18])[CH2:13][NH:14][CH:15]2[CH2:17][CH2:16]2)=[CH:6][C:5]=1[Br:19]>O1CCCC1.O>[NH2:3][C:4]1[C:9]([C:10]#[N:11])=[CH:8][C:7]([CH:12]([OH:18])[CH2:13][NH:14][CH:15]2[CH2:16][CH2:17]2)=[CH:6][C:5]=1[Br:19]
Reactant: N#Cc1cc(C(=O)CNC2CC2)cc(Br)c1N
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: N#Cc1cc(C(O)CNC2CC2)cc(Br)c1N
Reaction time: 1 h

Procedure:
3 gm of sodium borohydride were added at room temperature to a solution of 7.5 gm of 4'-amino-3'-bromo-5'-cyano-2-cyclopropylamino-acetophenone in 200 ml of tetrahydro-furan and 100 ml of water, and the mixture was stirred for one hour. Thereafter, the excess sodium borohydride was destroyed by addition of acetone. The insoluble part of the mixture was filtered off, and the solvents were distilled out of the filtrate in vacuo. The residue was dissolved in hot isopropanol, and the hydrochloride of 1-(4'-amino-3'-bromo-5'-cyano-phenyl)-2-cyclopropylanino-ethanol was precipitated by addition of isopropanolic hydrochloric acid, and recrystallized from isopropanol. M.p. 190°-193° C. (decomp.).