Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].C(=O)([O-])[O-].[K+].[K+].Br[CH2:17][C:18]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[C:19]=1[C:20]#[N:21]>CN(C)C=O.N1C=CC=CC=1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][C:18]2[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[C:19]=2[C:20]#[N:21])=[CH:4][C:3]=1[CH3:9]
Reactant: N#Cc1c(CBr)cccc1[N+](=O)[O-]
Reactant: Cc1cc(O)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(OCc2cccc([N+](=O)[O-])c2C#N)ccc1Cl
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 57.7 %

Procedure:
4-Chloro-3-methylphenol (0.12 g, 0.83 mmol) and potassium carbonate were added to a cooled (0° C.) and stirred solution of 2-bromomethyl-6-nitrobenzonitrile [W. T. Ashton and J. B. Hynes, J. Med. Chem, 16, 1233 (1973)] (0.2 g, 0.83 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 1.5 hours, then diluted with pyridine (1.5 mL), water, stirred for 1 hour, filtered and dried to yield 145 mg of 2-(4-chloro-3-methylphenoxymethyl)-6-nitrobenzonitrile.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([NH2:9])=[C:4]([Cl:10])[N:3]=1.[CH:11](O)=[O:12].C1(C)C=CC=CC=1.O>>[NH2:9][C:5]1[C:4]([Cl:10])=[N:3][C:2]([NH:1][CH:11]=[O:12])=[N:7][C:6]=1[Cl:8]
Reactant: O=CO
Reactant: Nc1nc(Cl)c(N)c(Cl)n1
Solvent: Cc1ccccc1
Solvent: O
Product: Nc1c(Cl)nc(NC=O)nc1Cl
Temperature: 2.5 °C
Yield: 1000 %

Procedure:
A solution of 2,5-diamino-4,6-dichloro-pyrimidine (0.001 mol; 2.0 g) and 98% strength formic acid (0.5 mol, 22.96 g, 18.8 ml) was stirred overnight at room temperature. Toluene (0.94 mol, 86.76 g, 18.82 ml) was then added and the reaction was cooled to 0-5° C. The product was filtered off and washed with water (1.11 mol, 20.0 g, 20.0 ml). The product was subsequently dried at 50° C. in vacuo. N-(5-Amino-4,6-dichloropyrimidin-2-yl)formamide was detected in the 1H NMR as a single product. 0.01 mol (1.62 g) of the abovementioned product was obtained, corresponding to a yield of about 70%.
Reaction SMILES: CC1(C)CC(C2C=CC=CC=2)N([C:13](=[O:30])[CH2:14][NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:20]=2)=[O:17])C1(C(N1CCCCC1)=O)C([O-])=O.[CH3:43][C:44]1([CH3:66])[CH2:49][CH2:48][CH2:47][N:46]([C:50]([CH:52]2[CH:56]([C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)[NH:55][CH:54]([C:63]([O-:65])=[O:64])[CH2:53]2)=[O:51])[CH2:45]1.N(C1[CH:71]=[C:72]([CH:78]=CC=1)[C:73](OCC)=O)=C=O>O1CCCC1>[CH3:43][C:44]1([CH3:66])[CH2:49][CH2:48][CH2:47][N:46]([C:50]([CH:52]2[CH:56]([C:57]3[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=3)[N:55]([C:13](=[O:30])[CH2:14][NH:15][C:16]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:20]=3)=[O:17])[CH:54]([C:63]([O:65][C:72]([CH3:78])([CH3:73])[CH3:71])=[O:64])[CH2:53]2)=[O:51])[CH2:45]1
Reactant: CCOC(=O)c1cccc(NC(=O)NCC(=O)N2C(c3ccccc3)CC(C)(C)C2(C(=O)[O-])C(=O)N2CCCCC2)c1
Reactant: CCOC(=O)c1cccc(N=C=O)c1
Reactant: CC1(C)CCCN(C(=O)C2CC(C(=O)[O-])NC2c2ccccc2)C1
Solvent: C1CCOC1
Product: CCOC(=O)c1cccc(NC(=O)NCC(=O)N2C(C(=O)OC(C)(C)C)CC(C(=O)N3CCCC(C)(C)C3)C2c2ccccc2)c1

Procedure:
B tert-Butyl (2RS,4SR,5SR)-4-(3,3-dimethylpiperidinocarbonyl-1-{2-[3-(3-(ethoxycarbonyl)phenyl]ureido]acetyl}-5-phenylpyrrolidine-2-carboxylate can be prepared as described in Example 17B, but from 2.7 g of tert-butyl (2RS,4SR,5SR)-1-(2-aminoacetyl)-4-(4-(3,3-dimethylpiperidinocarbonyl)-5-phenylpyrrolidine-2-carboxylate and 1.17 g of ethyl 3-isocyanatobenzoate in 120 cm3 of tetrahydrofuran. After treatment, there are obtained 2.3 g of tert-butyl (2RS,4SR,5SR)-4-(3,3-dimethylpiperidinocarbonyl)-1-{2-[3-(3-(ethoxycarbonyl)phenyl]ureido]acetyl}-5-phenylpyrrolidine-2-carboxylate in the form of a foam used as is in the subsequent syntheses.
Reaction SMILES: Br[C:2]1[N:10]2[C:5]([CH:6]=[N:7][C:8]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH:13]=3)=[N:9]2)=[CH:4][CH:3]=1.[OH:25][CH2:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1>>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:14]2[CH:13]=[C:12]([NH:11][C:8]3[N:7]=[CH:6][C:5]4=[CH:4][CH:3]=[C:2]([C:31]5[CH:32]=[C:27]([CH2:26][OH:25])[CH:28]=[CH:29][CH:30]=5)[N:10]4[N:9]=3)[CH:17]=[CH:16][CH:15]=2)[CH2:19][CH2:20]1
Reactant: CN1CCN(c2cccc(Nc3ncc4ccc(Br)n4n3)c2)CC1
Reactant: OCc1cccc(B(O)O)c1
Product: CN1CCN(c2cccc(Nc3ncc4ccc(-c5cccc(CO)c5)n4n3)c2)CC1
Yield: 19.1 %

Procedure:
Analogous to Example 1504, (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-[3-(4-methyl-piperazin-1-yl)-phenyl]-amine (0.0731 g, 0.189 mmol) and (3-Hydroxymethylphenyl)boronic acid (0.0513 g, 0.338 mmol) were reacted to afford (3-{2-[3-(4-Methyl-piperazin-1-yl)-phenylamino]-pyrrolo[2,1-f][1,2,4]triazin-7-yl}-phenyl)-methanol as a yellow powder (15 mg, 20%). LCMS: 415 (M+H); 1H-NMR (CDCl3): 8.70 (s, 1H), 8.21 (s, 1H), 7.92 (s, 1H), 7.62 (d, 1H, J=6.96 Hz), 7.49 (m, 2H), 7.20 (t, 1H, J=8.19 Hz), 6.93 (d, 1H, J=4.50 Hz), 6.88 (s, 1H), 6.84 (d, 1H, J=4.50 Hz), 6.87 (d, 1H, J=8.19 Hz), 4.77 (s, 2H), 2.98 (t, 4H, J=4.96 Hz), 2.44 (t, 4H, J=4.96 Hz), 2.34 (s, 3H).
Reaction SMILES: [OH:1][C:2]1[C:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])=[CH:5][N:4]([CH3:12])[N:3]=1.Cl[CH2:14][C:15]1[CH:34]=[CH:33][C:18]([O:19][CH2:20][C:21]2[N:22]=[C:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[O:24][C:25]=2[CH3:26])=[C:17]([O:35][CH3:36])[CH:16]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:36][O:35][C:17]1[CH:16]=[C:15]([CH:34]=[CH:33][C:18]=1[O:19][CH2:20][C:21]1[N:22]=[C:23]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[O:24][C:25]=1[CH3:26])[CH2:14][O:1][C:2]1[C:6]([CH2:7][C:8]([O:10][CH3:11])=[O:9])=[CH:5][N:4]([CH3:12])[N:3]=1
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2ccccc2)oc1C
Reactant: COC(=O)Cc1cn(C)nc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)Cc1cn(C)nc1OCc1ccc(OCc2nc(-c3ccccc3)oc2C)c(OC)c1
Temperature: 60 °C
Reaction time: 5 h
Yield: 57.2 %

Procedure:
A mixture of methyl (3-hydroxy-1-methyl-1H-pyrazol-4-yl)acetate (340 mg), 4-(4-chloromethyl-2-methoxyphenoxymethyl)-5-methyl-2-phenyloxazole (687 mg), potassium carbonate (553 mg) and N,N-dimethylformamide (10 ml) was stirred at 60° C. for 5 hrs. The reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and methyl [3-[3-methoxy-4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxy]-1-methyl-1H-pyrazol-4-yl]acetate (546 mg, yield 57%) was obtained as a colorless oil from a fraction eluted with ethyl acetate-hexane (2:1, volume ratio).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[N:3]=1.Cl.[CH:11]12[NH:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][O:13][CH2:12]2.C(N(CC)CC)C>CCO>[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH:11]3[CH2:17][CH2:16][CH:15]2[CH2:14][O:13][CH2:12]3)[CH:5]=[C:6]([Cl:8])[N:7]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: C1CC2COCC1N2
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: Clc1cc(N2C3CCC2COC3)nc(Cl)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 75.3 %

Procedure:
In a 250 mL round-bottomed flask was placed 2,4,6-trichloropyrimidine (8, 0.575 mL, 5 mmol) in EtOH (20 mL) to give a colorless solution. 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (33, 748 mg, 5.00 mmol) was added and the solution was cooled to 0° C. Triethylamine (2.091 mL, 15 mmol) was added slowly and the mixture was allowed to slowly warm to room temperature. The mixture was stirred at room temperature for one hour and was then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with sat NaHCO3. The organic phase was dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with ethyl acetate in hexanes (5-20%) to give the title compound (980 mg, 75%) as a white solid.
Reaction SMILES: BrC(Br)(Br)Br.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([I:17])=[CH:14][CH2:15]O)=[CH:9][CH:8]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)C(C)C)(C)C.[SH:46][C:47]1[CH:59]=[CH:58][C:50]([O:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])=[C:49]([CH3:60])[CH:48]=1>C(Cl)Cl>[Br:6][C:7]1[CH:12]=[CH:11][C:10](/[C:13](/[I:17])=[CH:14]/[CH2:15][S:46][C:47]2[CH:59]=[CH:58][C:50]([O:51][CH2:52][C:53]([O:55][CH2:56][CH3:57])=[O:54])=[C:49]([CH3:60])[CH:48]=2)=[CH:9][CH:8]=1
Reactant: OCC=C(I)c1ccc(Br)cc1
Reactant: CCOC(=O)COc1ccc(S)cc1C
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)COc1ccc(SC/C=C(\I)c2ccc(Br)cc2)cc1C
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.2 %

Procedure:
A solution of tetrabromomethane (2.1 g, 6.6 mmol) in dry methylene chloride (20 mL) was added dropwise to an ice-cooled solution of 3-(4-bromophenyl)-3-iodoprop-2-en-1-ol (1.5 g, 4.4 mmol) and triphenylphosphine (2.4 g, 9.0 mmol) in dry methylene chloride (50 mL). The reaction mixture was stirred at room temperature for 2 h and the solvent was evaporated in vacuo. Under nitrogen atmosphere, N,N-diisopropylethylamine (1.2 g, 9.0 mmol) and ethyl (4-mercapto-2-methylphenoxy)acetate (1.5 g, 6.6 mmol; Bioorg. Med. Chem. Lett. 2003, 13, 1517) were added to the residue. The reaction mixture was stirred for 3 h, filtered through a short path of silica gel and the filtrate was evaporated in vacuo. The residue was purified by column chromatography (silica gel Merck 60, hexane/ethyl acetate 1:0–9:1) giving 0.80 g of the ester. Yield: 0.80 g (40%).
Reaction SMILES: [P:1](Cl)([O:6][CH2:7][CH3:8])([O:3][CH2:4][CH3:5])=[O:2].[CH2:10]([NH2:12])[CH3:11]>ClC(Cl)C>[CH2:10]([NH:12][P:1](=[O:2])([O:6][CH2:7][CH3:8])[O:3][CH2:4][CH3:5])[CH3:11]
Reactant: CCN
Reactant: CCOP(=O)(Cl)OCC
Solvent: CC(Cl)Cl
Product: CCNP(=O)(OCC)OCC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.4 %

Procedure:
To a solution of 5.0 g (29.0 mmol) of diethyl chlorophosphate in 70 mL dichloroethane cooled on an ice bath was added 4.1 g (63.8 mmol) of ethylamine (70% aq). The mixture was allowed to stir at RT for 30 min and was then partitioned between ether and water. The organic layer was washed with brine, dried (MgSO4), and was filtered. The filtrate was evaporated in vacuo and the residue was kugelrohr distilled (0.8 torr, 90° C.) to yield 2.7 g (52%) of diethyl N-ethylphosphoramidate as a colorless oil.
Reaction SMILES: O.[OH-].[Li+].[C:4]([NH:12][CH:13]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([NH:36][C:37]([NH2:39])=[NH:38])[CH:31]=2)(=[O:29])=[O:28])[CH:21]=1)[CH2:14][C:15]([O:17]CC)=[O:16])(=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>O.C1COCC1>[C:4]([NH:12][CH:13]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([NH:26][S:27]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([NH:36][C:37]([NH2:39])=[NH:38])[CH:31]=2)(=[O:29])=[O:28])[CH:21]=1)[CH2:14][C:15]([OH:17])=[O:16])(=[O:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: CCOC(=O)CC(NC(=O)c1ccccc1)c1cccc(NS(=O)(=O)c2cccc(NC(=N)N)c2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: N=C(N)Nc1cccc(S(=O)(=O)Nc2cccc(C(CC(=O)O)NC(=O)c3ccccc3)c2)c1
Temperature: 25 °C
Reaction time: 20 h
Yield: 55 %

Procedure:
94 mg of lithium hydroxide monohydrate were added to a solution of 298.5 mg of (4f) in 30 ml of water and 30 ml of THF. The reaction mixture was stirred at room temperature for 20 h and then concentrated. Chromatographic purification on silica gel (acetonitrile/water=7:1) afforded a white solid (yield: 155 mg).
Reaction SMILES: [CH:1](/[C@H:7]1[O:11][C:10]([CH3:13])([CH3:12])[O:9][C@H:8]1[CH2:14][O:15][CH2:16][C:17]([OH:19])=[O:18])=[CH:2]\[CH:3]=[CH:4]\[C:5]#[CH:6].[CH3:20][Si](C=[N+]=[N-])(C)C.[N+](=C)=[N-].C(O)(=O)C>C1COCC1.CCOCC>[CH:1](/[C@H:7]1[O:11][C:10]([CH3:13])([CH3:12])[O:9][C@H:8]1[CH2:14][O:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:2]\[CH:3]=[CH:4]\[C:5]#[CH:6]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: C#C/C=C/C=C/[C@H]1OC(C)(C)O[C@H]1COCC(=O)O
Agent: C=[N+]=[N-]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CC(=O)O
Product: C#C/C=C/C=C/[C@H]1OC(C)(C)O[C@H]1COCC(=O)OC

Procedure:
A solution of 2-[[(4S,5R)-5-[(1E,3E)-1,3-hexadien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid in THF was cooled in an ice bath and treated with a solution of trimethylsilyldiazomethane in THF in portions. Excess diazomethane was decomposed with acetic acid and the mixture was diluted with ether and washed with water, saturated sodium bicarbonate, water (2×), and brine, dried, treated with silica gel and concentrated. Purification by chromatography on silica gel using a gradient of ether in hexane gave 0.9 g of 2-[[(4S,5R)-5-[(1E,3E)-1,3-hexadien-5-ynyl]-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester, a compound of formula (W), as an oil: 1H NMR (CDCl3) δ 1.37 (s, 3H), 1.51 (s, 3H), 3.06 (s, 1H), 3.49 (m, 2H), 3.74 (s, 3H), 4.16 (m, 2H), 4.42 (m, 1H), 4.65 (t, 1H), 5.60 (dd, 1H), 5.79 (dd, 1H), 6.33 (dd, 1H), 6.65 (dd, 1H) ppm.
Reaction SMILES: [Br-].[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH2:12][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].[Li]CCCC.[CH:37]([C:40]1[CH:41]=[C:42]([CH:46]([CH3:50])[CH2:47][CH:48]=O)[CH:43]=[CH:44][CH:45]=1)([CH3:39])[CH3:38].O>C1COCC1>[CH:37]([C:40]1[CH:41]=[C:42]([CH:46]([CH3:50])[CH2:47][CH:48]=[CH:12][C:6]2[CH:7]=[CH:8][C:9]([O:10][CH3:11])=[C:4]([O:3][CH3:2])[CH:5]=2)[CH:43]=[CH:44][CH:45]=1)([CH3:39])[CH3:38]
Reactant: CC(C)c1cccc(C(C)CC=O)c1
Reactant: COc1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1OC
Agent: [Br-]
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(C=CCC(C)c2cccc(C(C)C)c2)cc1OC
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 82.3 %

Procedure:
A solution of (3,4-dimethoxyphenyl)methyltriphenylphosphonium bromide (4.93 g, 10.0 mmol, 1.0 equiv.) in THF (10 mL), was cooled to 0° C. After adding n-BuLi (1.6 M in hexanes, 6.3 mL, 10.0 mmol, 1.0 equiv.) at 0° C., the red suspension was stirred at 0° C. for 20 min. 3-(3-Isopropylphenyl)butanal (2.09 g, 11.0 mmol, 1.1 equiv.) in THF (11 mL) was added, and the mixture was stirred at 0° C.→25° C. for 16 h. After addition of H2O at 25° C., the aqueous layer was extracted with hexanes (2×), the combined organic phases were dried (MgSO4), filtered and the filtrate was concentrated. The residue was purified by flash chromatography on SiO2 (hexanes/EtOAc 99:1→4:1) to yield 2.67 g (82%) of the title compound as a colorless oil.
Reaction SMILES: [C:1]1([C:7](Cl)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH2:28]([O:35][CH2:36][CH:37]([OH:40])[CH2:38][OH:39])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(O)(C)(C)C>[CH2:28]([O:35][CH2:36][CH:37]([CH2:38][O:39][C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[OH:40])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: OCC(O)COCc1ccccc1
Solvent: CC(C)(C)O
Solvent: CCN(CC)CC
Product: OC(COCc1ccccc1)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Yield: 80.1 %

Procedure:
To a stirred suspension of triphenylmethyl chloride (59.6 g, 0.21 mol) and triethylamine (32.6 mL, 0.23 mol) in tert-butyl alcohol (80 mL) at 60° C. was added a solution of 1-benzyloxy-2,3-propanediol (37.1 g, 0.20 mol) in tert-butyl alcohol (20 mL). The reaction was heated at reflux for 24 hours. The reaction mixture was evaporated to dryness, then purified using flash chromatography (0 to 30% EtOAc in hexanes) to afford the title compound (68 g, 75%) as an oil. m/z not found, r.t.=4.32 mins. 1H NMR (400 MHz; CDCl3) δ 7.46-7.41 (6H, m), 7.36-7.22 (14H, m), 4.52 (2H, s), 4.02-3.95 (1H, m), 3.63-3.54 (2H, m), 3.26-3.18 (2H, m), 2.40 (1H, s).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7](=[O:23])[NH:8][CH2:9][CH2:10][C:11]2[N:12]=[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[O:14][C:15]=2[CH3:16])=[C:5]([C:24](O)=[O:25])[CH:4]=[N:3]1.Cl.[F:28][CH:29]1[CH2:32][NH:31][CH2:30]1>>[CH3:16][C:15]1[O:14][C:13]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)=[N:12][C:11]=1[CH2:10][CH2:9][NH:8][C:7]([C:6]1[N:2]([CH3:1])[N:3]=[CH:4][C:5]=1[C:24]([N:31]1[CH2:32][CH:29]([F:28])[CH2:30]1)=[O:25])=[O:23]
Reactant: Cc1oc(-c2ccccc2)nc1CCNC(=O)c1c(C(=O)O)cnn1C
Reactant: FC1CNC1
Agent: Cl
Product: Cc1oc(-c2ccccc2)nc1CCNC(=O)c1c(C(=O)N2CC(F)C2)cnn1C

Procedure:
The product was obtained starting from 1-methyl-5-(2-(5-methyl-2-phenyloxazol-4-yl)ethylcarbamoyl)-1H-pyrazole-4-carboxylic acid (40 mg, 113 μmol) and 3-fluoroazetidine hydrochloride (15.1 mg, 135 μmol) according to the method described in example 37, step 3 as white solid (39 mg, 94.8 μmol, 84.0%).
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]([OH:22])(=O)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>O>[C:5]([Cl:3])(=[O:22])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]/[CH:13]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: O=S(Cl)Cl
Reactant: CCCCCC/C=C\CCCCCCCC(=O)O
Solvent: O
Product: CCCCCC/C=C\CCCCCCCC(=O)Cl
Temperature: 40 °C
Reaction time: 0.92 h

Procedure:
In a dry 2-necked, round bottomed flask, equipped with a magnetic stirrer and fixed with a separatory funnel, containing 13.15 ml (180 mmol) of thionyl chloride, and a water condenser, is placed 28.45 ml (100 mmol) of palmitoleic acid. Addition of the thionyl chloride is completed with heating to about 40° C. over the course of about 30 minutes. When addition of the thionyl chloride is complete the mixture is heated and stirred for an additional 55 minutes. The water condenser is then replaced with a distillation side arm condenser and the crude mixture is distilled. The crude distillate in the receiving flask is then fractionally distilled to obtain the acyl chloride, (Z)-hexadec-9-enoyl chloride. This acyl chloride, 10.95 g (40 mmol), is put into a dry separatory funnel and combined with 75 ml of dry dichloromethane for use in the next step of the reaction.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH:13]([OH:26])[CH2:14][O:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]([O:24]C)=[O:23])=[CH:18][CH:17]=3)=[CH:10][C:9]=2[CH:27]=1)([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO.O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([CH:13]([OH:26])[CH2:14][O:15][C:16]3[CH:17]=[CH:18][C:19]([C:22]([OH:24])=[O:23])=[CH:20][CH:21]=3)=[CH:10][C:9]=2[CH:27]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccc(OCC(O)c2cc3cc(C(C)(C)C)ccc3o2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC(C)(C)c1ccc2oc(C(O)COc3ccc(C(=O)O)cc3)cc2c1
Yield: 82 %

Procedure:
5-tert-Butyl-2-[1-hydroxy-2-(4-methoxycarbonylphenoxy)ethyl]benzofuran (112 g) obtained in Example 1 was dissolved in 1.5 liters of methanol, a solution of 24.3 g of sodium hydroxide dissolved in 400 ml of water was added thereto and the mixture was heated to reflux for 2 hours. The reaction mixture was concentrated in vacuo, ice water was added to the residue and the mixture was acidified with concentrated hydrochloric acid to give crystals. The crystals collected by filtration were dissolved in ethyl acetate, the solution was washed with water and dried over anhydrous magnesium sulfate followed by concentrating in vacuo whereupon the residue is crystallized. This was dried and recrystallized from acetonitrile to give 88.3 g of crystals. M.p. 175°-177° C.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([NH2:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:18])[C:6]=2[C:5]([NH:19][CH2:20][CH2:21][CH2:22][N:23]([CH3:25])[CH3:24])=[CH:4][C:3]=1[O:26][CH3:27].N[C:29]1C2C(=O)C3C(=C(N)C=CC=3)C(=O)C=2C(NCCCN(C)C)=CC=1S(O)(=O)=O.[OH-].[K+].[CH3:59][O:60][S:61]([O:64]C)(=[O:63])=[O:62]>O.COCCOCCOC>[CH3:59][O:60][S:61]([O-:64])(=[O:63])=[O:62].[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[C:9]([NH2:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=[O:18])[C:6]=2[C:5]([NH:19][CH2:20][CH2:21][CH2:22][N+:23]([CH3:29])([CH3:25])[CH3:24])=[CH:4][C:3]=1[O:26][CH3:27]
Reactant: CN(C)CCCNc1cc(S(=O)(=O)O)c(N)c2c1C(=O)c1c(N)cccc1C2=O
Reactant: COS(=O)(=O)OC
Reactant: COc1cc(NCCCN(C)C)c2c(c1N)C(=O)c1cccc(N)c1C2=O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: COCCOCCOC
Product: COS(=O)(=O)[O-]
Product: COc1cc(NCCC[N+](C)(C)C)c2c(c1N)C(=O)c1cccc(N)c1C2=O
Reaction time: 3 h

Procedure:
2.44 parts of 1,5-diamino-4-(3-dimethylamino-propylamino)-2-methoxy-anthraquinone prepared from 1,5-diamino-4-(3-dimethylamino-propylamino)-9,10-dioxo-9,10-dihydro-anthracene-2-sulfonic acid and methanolic potassium hydroxide at 95° C. were dispersed in 50 parts of diglyme and treated with 0.75 part of dimethylsulfate. The reaction mixture was kept for 3 hours at room temperature. The precipitate was filtered off and washed with acetone. Upon drying 2.8 parts of the dye of formula Iz were obtained. The blue dye Iz is very good water-soluble. The analytic data are consistent with the assigned structure for dye Iz.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[N:9]=[C:8]([O:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:22])([F:21])[F:20])[CH:13]=3)[N:7](COCC[Si](C)(C)C)[C:6]=2[C:5](=[O:31])[N:4]([CH2:32][CH2:33][O:34][CH2:35][CH2:36][O:37]C2CCCCO2)[C:3]1=[O:44].Cl>C(O)C>[OH:37][CH2:36][CH2:35][O:34][CH2:33][CH2:32][N:4]1[C:5](=[O:31])[C:6]2[NH:7][C:8]([O:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:21])([F:22])[F:20])[CH:13]=3)=[N:9][C:10]=2[N:2]([CH3:1])[C:3]1=[O:44]
Reactant: Cn1c(=O)n(CCOCCOC2CCCCO2)c(=O)c2c1nc(Oc1cccc(OC(F)(F)F)c1)n2COCC[Si](C)(C)C
Agent: Cl
Solvent: CCO
Product: Cn1c(=O)n(CCOCCO)c(=O)c2[nH]c(Oc3cccc(OC(F)(F)F)c3)nc21
Yield: 84.1 %

Procedure:
To a solution of 3-methyl-1-(2-(2-(tetrahydro-2H-pyran-2-yloxy)ethoxy)ethyl)-8-(3-(trifluoromethoxy)phenoxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-1H-purine-2,6(3H,7H)-dione (0.64 g, 1.16 mmol,) in ethanol (15 mL) was added HCl (3 mL); then it was refluxed overnight. The solvent was concentrated to give a crude product which was purified by a column chromatography to give 1-(2-(2-hydroxyethoxy)ethyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (420 mg, 84% yield) as a white solid. LCMS retention time 1.209 min, LCMS MH+ 431.
Reaction SMILES: [CH3:1][C:2]1[NH:10][C:9]2[CH:8]=[CH:7][NH:6][C:5](=O)[C:4]=2[C:3]=1[CH3:12].P(Cl)(Cl)([Cl:15])=O>>[Cl:15][C:5]1[C:4]2[C:3]([CH3:12])=[C:2]([CH3:1])[NH:10][C:9]=2[CH:8]=[CH:7][N:6]=1
Reactant: Cc1[nH]c2cc[nH]c(=O)c2c1C
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1[nH]c2ccnc(Cl)c2c1C
Temperature: 25 °C
Reaction time: 6 h
Yield: 43 %

Procedure:
2,3-dimethyl-1,5-dihydro-pyrrolo[3,2-c]pyridin-4-one (6.0 g, 37.0 mmol) prepared in Step 3 was added to phosphorus oxychloride (230 ml). The reaction mixture was refluxed under stirring for 6 hours, cooled to room temperature, and then concentrated under reduced pressure. The resulting residue was dissolved in methanol (200 ml). The obtained solution was alkalized with a saturated ammonia solution in methanol and concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate) and recrystallized with ether to give the titled compound as a pale yellow solid. (Yield: 43.0%)