Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[I-:2].C([O-])(=O)C.[NH4+].C(OO)(=O)C.C([Sn](CCCC)(CCCC)[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1)CCC>O.CO.C(#N)C>[I:2][C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C=O)cc1
Reactant: [I-]
Agent: CC(=O)OO
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC#N
Solvent: O
Solvent: CO
Product: O=Cc1ccc(I)cc1
Reaction time: 0.33 h
Yield: 48 %

Procedure:
To 5.2 μL sodium [123I] iodide (138.1 MBq) was added, ammonium acetate buffer (100 μL, pH 4, 0.2M), sodium [127I] iodide (51 μL, 10 mM solution in 0.01M sodium hydroxide, 5.1×10−7 moles), peracetic acid (11 μL, 50 mM solution, 5.5×10−7 moles) and 4-tributylstannyl benzaldehyde (100 μL, 200 μg, 2 mg/mL solution in acetonitrile, 5.06×10−7 moles). An additional 50 μL acetonitrile was added to aid solubility of the 4-tributylstannyl benzaldehyde, and the reaction mixture allowed to incubate at room temperature for approximately 20 minutes prior to HPLC analysis, which showed [123I]-4-iodobenzaldehyde (tR˜8 minutes, system A, Example 2) with an RCP of >90%. To the reaction mixture was added 1 mL acetonitrile and 10 mL water and the resulting solution loaded onto a tC-18 light cartridge (pre-treated with 2.5 mL methanol and 5 mL water). [123I]-4-iodobenzaldehyde was eluted with 0.5 mL 1:1 t-butanol:water in 48% yield (non-decay corrected).
Reaction SMILES: [CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25]([NH:27][NH:28][C:29](NC)=[O:30])=[S:26].Cl>>[CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25]1[S:26][C:29](=[O:30])[NH:28][N:27]=1
Reactant: CNC(=O)NNC(=S)N1N=C(c2ccc([N+](=O)[O-])cc2)c2cc3c(cc2CC1C)OCO3
Agent: Cl
Product: CC1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1c1n[nH]c(=O)s1)OCO3
Temperature: 80 °C
Yield: 70.2 %

Procedure:
A mixture of 2.14 g (4.69 mmol) of the starting material XXX and 122 ml of concentrated hydrochloric acid was stirred at 80° C. A solid material precipitated from the starting solution. The reaction mixture was concentrated to about half of its volume, diluted with 40 ml of water and made alkaline with sodium hydrogen carbonate solution. The precipitated product was filtered off and washed with water to yield 1.40 g (70%) of the title compound. Mp.: 288° C.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[O:15])[C@H:6]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[NH2:7])[CH3:3].[O-]S([O-])(=O)=O.[Mg+2].[CH:22](=O)[CH3:23].CCN(CC)CC.[BH4-].[Na+]>CO.C1COCC1>[CH2:22]([NH:7][C@@H:6]([CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:5]([O:4][CH2:2][CH3:3])=[O:15])[CH3:23]
Reactant: CC=O
Reactant: CCOC(=O)[C@@H](N)Cc1ccccc1
Agent: Cl
Agent: O=S(=O)([O-])[O-]
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCN(CC)CC
Product: CCN[C@@H](Cc1ccccc1)C(=O)OCC
Yield: 46.7 %

Procedure:
Synthesized according to the general procedure as described in Example 1a using L-phenylalanine ethyl ester hydrochloride (2 gm, 8.7 mmol), THF (25 mL), MgSO4 (1.77 gm, 14.79 mmol), acetaldehyde (983 μL, 17.4 mmol), Et3N (1.21 mL, 8.7 mmol), sodium borohydride (658 mg, 17.4 mmol), and methanol (30 mL) to give 11h (900 mg, 47%) in FIG. 2. 1H NMR (500 MHz, CDCl3): δ 1.1 (3H, t, J=7.13 Hz), 1.15 (3H, t, J=7.13 Hz), 1.42-1.7 (1H, bs), 2.46-2.73 (2H, m), 2.96 (2H, dq, J=7.44, 13.42 Hz), 3.53 (1H, t, J=6.88 Hz), 4.1 (2H, q, J=7.13 Hz), 7.16-7.38 (5H, m). ESI-MS: 244.1 (M+23).
Reaction SMILES: [C@H:1]12[CH2:6][C@H:5]1[CH2:4][C@@H:3]([CH2:7][NH:8][C:9]([C:11]1[CH:12]=[CH:13][CH:14]=[C:15]3[O:19][CH:18]=[CH:17][C:16]=13)=[O:10])[NH:2]2.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33](O)=[O:34])=[CH:23][CH:22]=1>>[F:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[S:31][C:30]([CH3:32])=[N:29][C:28]=2[C:33]([N:2]2[C@H:3]([CH2:7][NH:8][C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[O:19][CH:18]=[CH:17][C:16]=34)=[O:10])[CH2:4][C@H:5]3[C@@H:1]2[CH2:6]3)=[O:34])=[CH:25][CH:26]=1
Reactant: O=C(NC[C@@H]1C[C@@H]2C[C@@H]2N1)c1cccc2occc12
Reactant: Cc1nc(C(=O)O)c(-c2ccc(F)cc2)s1
Product: Cc1nc(C(=O)N2[C@H](CNC(=O)c3cccc4occc34)C[C@@H]3C[C@@H]32)c(-c2ccc(F)cc2)s1

Procedure:
prepared by reaction of benzofuran-4-carboxylic acid [(1S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid. LC-MS (basic): tR=1.38 min; [M+H]+=476.1.
Reaction SMILES: Br.C([O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][CH:17]([O:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:12][CH:11]=1)C1C=CC=CC=1>C(O)(=O)C>[F:30][C:27]1[CH:28]=[CH:29][C:24]([O:23][CH:17]([CH2:16][C:13]2[CH:12]=[CH:11][C:10]([OH:9])=[CH:15][CH:14]=2)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:25][CH:26]=1
Reactant: CCOC(=O)C(Cc1ccc(OCc2ccccc2)cc1)Oc1ccc(F)cc1
Agent: Br
Solvent: CC(=O)O
Product: CCOC(=O)C(Cc1ccc(O)cc1)Oc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 50.9 %

Procedure:
To a hydrogen bromide.acetic acid solution (25%, 70 ml) was added ethyl 3-(4-benzyloxyphenyl)-2-(4-fluorophenoxy)propionate (7.00 g) obtained from Reference example 25(a), and the reaction solution was stirred for 3 hours at room temperature. The reaction solution was concentrated under reduced pressure, then the residue was dissolved in ethanol (70 ml), and potassium carbonate (6.90 g) was added thereto followed by stirring for 4 hours at room temperature. The reaction solution was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and water. The separated ethyl acetate layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on a silica gel-column (eluant; hexane/ethyl acetate=9/1˜4/1) to give the target compound (2.75 g) as a white powder.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8](Br)=[CH:9][O:10][C:6]=2[CH:5]=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[NH2:1][C:2]1[C:7]2[C:8]([C:20]3[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][CH:21]=3)=[CH:9][O:10][C:6]=2[CH:5]=[CH:4][N:3]=1
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Reactant: Nc1nccc2occ(Br)c12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Nc1ccc(-c2coc3ccnc(N)c23)cc1
Temperature: 80 °C
Reaction time: 14 h
Yield: 84.2 %

Procedure:
The mixture of 4-amino-3-bromo-furo[3,2-c]pyridine (7) (63 mg, 0.29 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (84 mg, 0.38 mmol), Pd(PPh3)4 (34 mg, 0.029 mmol) and sodium carbonate (0.74 ml, 1.5 mmol) in 3 ml of DME was stirred for 14 hours at 80° C. The solvent was removed, and the resultant residue was purified by chromatography on a silica gel column gel to afford the titled compound (55 mg) 1H NMR (400 MHz, DMSO-d6) ppm 7.82 (d, J=6.1 Hz, 1H), 7.77 (s, 1H), 7.15 (d, J=8.3 Hz, 2H), 6.89 (d, J=5.8 Hz, 1H), 6.69 (d, J=8.3 Hz, 2H), 5.49 (s, 2H), 5.32 (s, 2H). MS: m/z 226 (M+H)+.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([N:7]2[CH2:12][CH2:11][CH:10]([NH:13][CH2:14][CH2:15][OH:16])[CH2:9][CH2:8]2)[S:5][CH:6]=1.[CH3:17][C:18]1([CH3:38])[C:27]2[C:22](=[CH:23][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:26]=2)[C:21](=[O:37])[CH2:20][CH2:19]1>>[OH:16][CH2:15][CH2:14][NH:13][CH:10]1[CH2:11][CH2:12][N:7]([C:4]2[S:5][CH:6]=[C:2]([C:24]3[CH:23]=[C:22]4[C:27]([C:18]([CH3:38])([CH3:17])[CH2:19][CH2:20][C:21]4=[O:37])=[CH:26][CH:25]=3)[N:3]=2)[CH2:8][CH2:9]1
Reactant: CC1(C)CCC(=O)c2cc(B3OC(C)(C)C(C)(C)O3)ccc21
Reactant: OCCNC1CCN(c2nc(Br)cs2)CC1
Product: CC1(C)CCC(=O)c2cc(-c3csc(N4CCC(NCCO)CC4)n3)ccc21

Procedure:
The preparation is carried out as already described above starting from 100 mg (0.27 mmol) of 2-[1-(4-bromothiazol-2-yl)piperidin-4-ylamino]ethanol (preparation already described above) and 88 mg (0.29 mmol) of 4,4-dimethyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-naphthalen-1-one. The product was purified by means of flash chromatography on silica gel.
Reaction SMILES: [CH2:1]([NH:3][OH:4])[CH3:2].[H-].[Na+].[Br:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[C:18]([CH2:21]Cl)=[N:19][N:20]=[C:16]3[CH2:15][N:14]=[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:12]=2[CH:29]=1>CN(C)C=O>[Br:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[C:18]([CH2:21][N:3]([CH2:1][CH3:2])[OH:4])=[N:19][N:20]=[C:16]3[CH2:15][N:14]=[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)[C:12]=2[CH:29]=1
Reactant: ClCc1nnc2n1-c1ccc(Br)cc1C(c1ccccn1)=NC2
Reactant: CCNO
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN(O)Cc1nnc2n1-c1ccc(Br)cc1C(c1ccccn1)=NC2

Procedure:
In the manner given in Example 16, a solution of N-ethylhydroxylamine in dimethylformamide is treated with sodium hydride suspended in mineral oil, and the mixture is treated with 8-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine to give 8-bromo-1-[(ethylhydroxyamino)methyl]-6-(2-pyridyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[S:3][C:4]1[CH:15]=[CH:14][C:7]([CH2:8][CH:9]([C:12]#[N:13])[C:10]#[N:11])=[CH:6][CH:5]=1.[H-].[Na+].[Cl:20][C:21]([CH2:23]Cl)=[CH2:22]>CN(C)C=O>[Cl:20][C:21](=[CH2:22])[CH2:23][C:9]([CH2:8][C:7]1[CH:6]=[CH:5][C:4]([S:3][C:2]([F:16])([F:1])[F:17])=[CH:15][CH:14]=1)([C:12]#[N:13])[C:10]#[N:11]
Reactant: C=C(Cl)CCl
Reactant: N#CC(C#N)Cc1ccc(SC(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=C(Cl)CC(C#N)(C#N)Cc1ccc(SC(F)(F)F)cc1
Yield: 46.5 %

Procedure:
Using 0.50 g of (4-(trifluoromethylthio)benzyl)malononitrile, 5 ml of N,N-dimethylformamide, 90 mg of sodium hydride (60% in oil), and 0.26 g of 2,3-dichloropropene, and according to the process described in the Production Example 1, there was obtained 0.30 g of 2-(2-chloro-2-propenyl)-2-(4-(trifluoromethylthio)benzyl)malononitrile (the present compound (2)).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[C@@H:14]([NH:15]C(=O)OC(C)(C)C)[CH2:13][C@@H:12]([N:23]2[CH2:30][C:29]3[C:25](=[N:26][NH:27][CH:28]=3)[CH2:24]2)[CH2:11][S:10]1.[C:31]([OH:37])([C:33]([F:36])([F:35])[F:34])=[O:32]>C(Cl)Cl>[F:34][C:33]([F:36])([F:35])[C:31]([OH:37])=[O:32].[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[C@@H:14]([NH2:15])[CH2:13][C@@H:12]([N:23]2[CH2:30][C:29]3[C:25](=[N:26][NH:27][CH:28]=3)[CH2:24]2)[CH2:11][S:10]1
Reactant: CC(C)(C)OC(=O)N[C@H]1C[C@@H](N2Cc3c[nH]nc3C2)CSC1c1cc(F)ccc1F
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@H]1C[C@@H](N2Cc3c[nH]nc3C2)CSC1c1cc(F)ccc1F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
tert-Butyl N-[(3S,5R)-2-(2,5-difluorophenyl)-5-(4,6-dihydro-2H-pyrrolo[3,4-c]pyrazol-5-yl)tetrahydrothiopyran-3-yl]carbamate (3.2 mg, 0.007 mmol) was dissolved in a mixture of TFA (0.5 mL) and methylene chloride (1.0 mL) and stirred at RT for 1 h. The solvents were evaporated and the residue was freeze-dried from a mixture of benzene and ethanol to give the title compound as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](Br)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].[CH:31]1(B(O)O)[CH2:33][CH2:32]1.C([O-])([O-])=O.[K+].[K+]>[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2].C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH:31]4[CH2:33][CH2:32]4)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2]
Reactant: OB(O)C1CC1
Reactant: CCOC(=O)c1cnn(-c2nc3ccc(Br)cc3c(=O)n2COCC[Si](C)(C)C)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Product: CCOC(=O)c1cnn(-c2nc3ccc(C4CC4)cc3c(=O)n2COCC[Si](C)(C)C)c1
Temperature: 80 °C
Yield: 26.1 %

Procedure:
A mixture of 1-[6-bromo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (0.500 g, 1.01 mmol), cyclopropylboronic acid (0.199 g, 2.32 mmol), dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium(II)dichloromethane adduct (0.100 g, 0.123 mmol), K2CO3 (0.420 g, 3.04 mmol) and THF (10 mL) were purged for 15 minutes with nitrogen and then heated to 80° C. for 15 h. The mixture was cooled to room temperature and filtered through a pad of CELITE®. The filtrate cake was washed with dichloromethane and concentrated. The residue was purified by FCC (0-20% EtOAc/hexanes) to yield the titled compound (0.120 g, 26% yield). MS (ESI/Cl): mass calcd. for C23H30N4O4Si, 454.2; m/z found, 455.2 [M+H]+.
Reaction SMILES: C(NC1C=CC(C2C=C3C(CN([C@@H](C(C)C)C(O)=O)C3=O)=CC=2)=CC=1)(=O)C1C=CC=CC=1.[CH3:33][O:34][C:35]1[CH:67]=[CH:66][CH:65]=[CH:64][C:36]=1[C:37]([NH:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]2[CH:54]=[C:53]3[C:49]([CH2:50][N:51]([C@@H:56]([CH:61]([CH3:63])[CH3:62])[C:57]([O:59]C)=[O:58])[C:52]3=[O:55])=[CH:48][CH:47]=2)=[CH:42][CH:41]=1)=[O:38]>>[CH3:33][O:34][C:35]1[CH:67]=[CH:66][CH:65]=[CH:64][C:36]=1[C:37]([NH:39][C:40]1[CH:41]=[CH:42][C:43]([C:46]2[CH:54]=[C:53]3[C:49]([CH2:50][N:51]([C@@H:56]([CH:61]([CH3:63])[CH3:62])[C:57]([OH:59])=[O:58])[C:52]3=[O:55])=[CH:48][CH:47]=2)=[CH:44][CH:45]=1)=[O:38]
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4OC)cc3)cc2C1=O
Agent: CC(C)[C@@H](C(=O)O)N1Cc2ccc(-c3ccc(NC(=O)c4ccccc4)cc3)cc2C1=O
Product: COc1ccccc1C(=O)Nc1ccc(-c2ccc3c(c2)C(=O)N([C@H](C(=O)O)C(C)C)C3)cc1
Yield: 84 %

Procedure:
The compound of example 160 was prepared analogous to compound of example 98 by hydrolysis of compound of example 159.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:16]=[C:15]([O:17]C)[C:14]([Cl:19])=[C:13]([Cl:20])[C:10]=3[S:11][CH:12]=2)=[CH:4][CH:3]=1.Cl.N1C=CC=CC=1>O>[Cl:19][C:14]1[C:15]([OH:17])=[CH:16][C:9]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[CH:12][S:11][C:10]=2[C:13]=1[Cl:20]
Reactant: COc1cc2c(-c3ccc(Cl)cc3)csc2c(Cl)c1Cl
Agent: Cl
Solvent: O
Solvent: c1ccncc1
Product: Oc1cc2c(-c3ccc(Cl)cc3)csc2c(Cl)c1Cl
Yield: 78.2 %

Procedure:
A mixture of 200 mg of 3-(4-chlorophenyl)-6,7-dichloro-5-methoxybenzo[b]thiophene and 1.77 g of pyridine hydrochloride is stirred and heated at 195°-205° for two and one half hours. The reaction is cooled and 20 ml of water is added. The resulting solid is collected on a filter and washed with 1N hydrochloric acid. The product is chromatographed on a silica gel-hexane column using 3:1 hexane/ether as elutent. The product is isolated and recrystallized from acetone-hexane to give 150 mg of 6,7-dichloro-3-(4-chlorophenyl)-5-hydroxybenzo[b]thiophene as a white powder, mp 174°-176°.
Reaction SMILES: [CH2:1]([N:19]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])C#N)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].O.[OH-].[Na+].C(Cl)(Cl)Cl>OS(O)(=O)=O>[CH2:22]([NH:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]
Reactant: CCCCCCCCCCCCCCCCCCN(C#N)CCCCCCCCCCCCCCCCCC
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCCCCCCCCCCCCCCCCCNCCCCCCCCCCCCCCCCCC
Reaction time: 1 h
Yield: 42.2 %

Procedure:
The crude dioctadecylcyanamide (38 g) was suspended in 2.75 M H2SO4 (150 mL) and the mixture was refluxed for 2.5 h. After cooling to room temperature H2O (100 mL), 30% NaOH (100 mL) and CHCl3 (300 mL) were added. The organic phase was separated, dried and evaporated. The solid residue was suspended in Et2O and stirred for 1 h. The solid was filtered and washed with to give the desired compound (15.3 g; 29.3 mmol). Yield 48%. K.F.: 0.20%. The 1H-NMR, 13C-NMR, MS and IR spectra were consistent with the structure.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[CH:13]=[CH:12][N:11]=[CH:10][N:9]2[C:14]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([I:22])=[CH:18][C:17]=1[F:23])=[O:5])C.O.[OH-].[Li+].Cl>O1CCOCC1.O>[F:23][C:17]1[CH:18]=[C:19]([I:22])[CH:20]=[CH:21][C:16]=1[NH:15][C:14]1[N:9]2[CH:10]=[N:11][CH:12]=[CH:13][C:8]2=[CH:7][C:6]=1[C:4]([OH:5])=[O:3]
Reactant: CCOC(=O)c1cc2ccncn2c1Nc1ccc(I)cc1F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)c1cc2ccncn2c1Nc1ccc(I)cc1F
Temperature: 60 °C

Procedure:
To a solution of 7-(2-fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ethyl ester (230 mg, 0.54 mmol) in a mixture of dioxane (2 mL) and water (1 mL) was added lithium hydroxide monohydrate (45 mg, 1.08 mmol). The reaction was heated at 60° C. for 1 hour. Aqueous hydrochloric acid (1M) was added dropwise until pH˜5 causing a precipitate to form. The reaction mixture was filtered and the solid residue washed with ethyl acetate (5 mL) to yield the title compound as an off white solid (67 mg, 31%). LCMS (Method B): RT=3.22 min, M+H+=398.
Reaction SMILES: [CH2:1]([OH:5])[CH2:2][C:3]#[CH:4].[O:6]1[CH:11]=[CH:10][CH2:9][CH2:8][CH2:7]1>CCCCCC>[O:6]1[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]1[O:5][CH2:1][CH2:2][C:3]#[CH:4]
Reactant: C#CCCO
Reactant: C1=COCCC1
Solvent: CCCCCC
Product: C#CCCOC1CCCCO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.9 %

Procedure:
A solution of 3-butyn-1-ol (3.0 g, 0.042 mol) and 3,4-dihydropyran (4.20 g, 0.05 mol) in hexane (10 ml) (Bongini et. al., Synthesis, 618, 1979), is added to a suspension of Dowex (1.5 g) in hexane (10 ml) and the mixture is stirred for 1 hr at room temperature. The resin is filtered off and the solvent removed in vacuo. The crude residue is purified by flash chromatography using hexane/ethyl acetate (9:1, v/v) to give 3-butyn-1-yl tetrahydropyranyl ether (6.47 g, 97%) as a colorless liquid: Rf=0.25; Hexane/ethyl acetate (1:1, v/v) IR (film) ν3300 (C≡C--H), 2160 (C≡C); and 1H NMR (CDCl3) δ1.48 (m, 6H), 1.88 (t, J=3 Hz, 1H), 2.35 (m, 2H), 3.60 (m, 4H), 4.56 (br S, 1H).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[C:15]([O:19][C:20]([CH2:22][NH:23][CH:24]1[CH2:28][CH2:27][C:26](=O)[CH2:25]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[CH3:30][CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(O)(=O)C.[OH-].[Na+].[ClH:43].C(OCC)C>ClCCCl>[ClH:43].[C:15]([O:19][C:20]([CH2:22][NH:23][C@H:24]1[CH2:28][CH2:27][C@@H:26]([N:34]2[CH2:35][CH2:36][CH:31]([CH3:30])[CH2:32][CH2:33]2)[CH2:25]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]
Reactant: CC(C)(C)OC(=O)CNC1CCC(=O)C1
Reactant: CC1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CC1CCN([C@@H]2CC[C@H](NCC(=O)OC(C)(C)C)C2)CC1
Temperature: 25 °C
Reaction time: 22 h
Yield: 35 %

Procedure:
Sodium triacetoxyborohydride (3.37 g, 15.9 mmol) was added to a solution of 3-[(tert-butyloxycarbonyl)methylamino]cyclopentan-1-one (2.42 g, 11.3 mmol), 4-methylpiperidine (1.2 ml, 10 mmol) and acetic acid (0.65 ml, 11 mmol) in 1,2-dichloroethane (40 ml). The resulting mixture was stirred at room temperature overnight (22 h). 1M Aqueous sodium hydroxide (100 ml) was added and the mixture extracted with dichloromethane (2×40 ml). The combined extracts were dried (MgSO4) and evaporated. The residue was dissolved in diethyl ether (40 ml) and treated with 1M hydrogen chloride in diethyl ether (10 ml, 10 mmol) to give a precipitate. The solid was collected under suction, washed with diethyl ether then isohexane and dried in vacuo (2.89 g). A portion of this solid (1.764 g) was recrystallized from methanol-ethyl acetate to afford the title product (0.7203 g, 35%) as a white solid; δH (400 MHz, CD3OD) 1.02 (3H, d, J 6.7 Hz), 1.39-1.41 (2H, m), 1.46 (9H, s), 1.71 (1H, m), 1.83-1.98 (6H, m), 2.14 (1H, m), 2.27 (1H, m), 2.82 (3H, s), 2.93 (2H, m), 3.50 (1H, m), 3.59 (2H, m), 4.44 (1H, m); m/z (ES+) 297 ([M+H]+), 241 (100%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([C:23]#[C:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1N=NC(Cl)=CC=1OCC1C=CC=CC=1)C1C=CC=CC=1.C(C1CCCCC1)#C>>[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([C:23]#[C:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C(#Cc1cc(OCc2ccccc2)c(OCc2ccccc2)nn1)c1ccccc1
Agent: C#CC1CCCCC1
Agent: Clc1cc(OCc2ccccc2)c(OCc2ccccc2)nn1
Product: C(#CC1CCCCC1)c1cc(OCc2ccccc2)c(OCc2ccccc2)nn1

Procedure:
Prepared as described for 3,4-bis(benzyloxy)-6-(phenylethynyl)pyridazine (Intermediate 2) from 3,4-bis(benzyloxy)-6-chloropyridazine (Intermediate 1) and ethynylcyclohexane.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[NH:7][C@:8]([CH2:26][OH:27])([CH3:25])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:1]([O:5][C:6](=[O:28])[NH:7][C@:8]([CH:26]=[O:27])([CH3:25])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:13][CH:12]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CCCCCCCOc1ccc(CC[C@](C)(CO)NC(=O)OC(C)(C)C)cc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Solvent: ClCCl
Product: CCCCCCCOc1ccc(CC[C@](C)(C=O)NC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of [(R)-1-hydroxymethyl-3-(4-heptyloxy-phenyl)-1-methyl-propyl]-carbamic acid tert-butyl ester (1.98 g, 5.03 mMol) in CH2Cl2 (20 ml) is added N-morpholine-N-oxide (884 mg, 7.54 mMol) and tetra-n-propylammonium perruthenate (177 mg, 0.50 mMol). The mixture is stirred at RT for 1 hour. The mixture is then filtered over a short pad of SiO2 eluting with diethyl ether. The filtrate is concentrated under reduced pressure to give the title compound. The crude product is sufficiently pure to be used in the next stage without further purification.