Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([C:14]2[C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=[CH:16][N:15]=2)=[O:13])=[C:4]1[CH3:23])[CH3:2].C(N1C2[C:29](=[CH:30][CH:31]=CC=2)[C:28]([C:35](C2C(C(O)=O)=NC=CC=2)=[O:36])=[C:27]1[CH3:46])C.C1([NH:53][C:54]2[CH:59]=[CH:58][CH:57]=[C:56]([CH3:60])[CH:55]=2)C=CC=CC=1>N1C=CC=CC=1>[C:35]([O:22][C:20](=[O:21])[CH3:19])(=[O:36])[CH3:28].[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2([NH:53][C:54]3[CH:59]=[CH:58][CH:57]=[C:56]([C:60]4[CH:46]=[CH:27][CH:28]=[CH:29][C:30]=4[CH3:31])[CH:55]=3)[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:19]3[C:20](=[O:21])[O:13]2)=[C:4]1[CH3:23])[CH3:2]
Reactant: CCn1c(C)c(C(=O)c2cccnc2C(=O)O)c2ccccc21
Reactant: CCn1c(C)c(C(=O)c2ncccc2C(=O)O)c2ccccc21
Reactant: Cc1cccc(Nc2ccccc2)c1
Solvent: c1ccncc1
Product: CC(=O)OC(C)=O
Product: CCn1c(C)c(C2(Nc3cccc(-c4ccccc4C)c3)OC(=O)c3cccnc32)c2ccccc21

Procedure:
Following a procedure similar to that described in Example 3 but employing 1.6 g. of an isomer mixture comprising 2-[(1-ethyl-2-methyl-3-indolyl)carbonyl]-3-pyridinecarboxylic acid and 3-[(1-ethyl-2-methyl-3-indolyl)carbonyl]-2-pyridinecarboxylic acid, 0.95 g. of N-phenyl-m-toluidine, 0.5 ml. of pyridine and 6 ml. of acetic anhydride there was obtained 7-(1-ethyl-2-methyl-3-indolyl)-7-(m-tolylphenylamino)furo[3,4-b]-pyridine-5(7H)-one as a yellow solid, m.p. 178°-190° C. (dec.). A toluene solution of the product contacted with acidic clay or phenolic resin developed an orange image.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.[Cu](C#N)[C:14]#[N:15]>CN(C)C=O.O>[O:12]=[C:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([C:14]#[N:15])[CH:11]=2)[CH:6]=[CH:7][NH:8]1
Reactant: O=c1[nH]ccc2ccc(Br)cc12
Reactant: N#C[Cu]C#N
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1ccc2cc[nH]c(=O)c2c1
Temperature: 180 °C
Yield: 70.1 %

Procedure:
To a suspension of 7-bromoisoquinolin-1(2H)-one (70 g, 0.31 mol) in N,N-dimethylformamide (1 L) was added copper cyanide (56 g, 0.63 mol). The reaction was heated to 180° C. for 2 hours. The reaction was cooled to room temperature and was diluted with water (1 L). The solution was extracted with ethyl acetate (3×). The organics were dried over sodium sulfate, filtered, and concentrated to give crude 1-oxo-1,2-dihydroisoquinoline-7-carbonitrile (37 g). This crude material was taken up in ethanol (500 mL) and 1 N aqueous sodium hydroxide (400 mL) was added. The mixture was heated to reflux and stirred for 2 hours. The reaction was cooled to room temperature and the pH was adjusted to ˜2 with 1 N aqueous hydrochloric acid. The solids were collected by filtration, rinsed with water, and dried under vacuum to give the title compound (35 g, 85%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6, δ): 13.15 (br. s., 1H), 11.49 (s, 1H), 8.75 (s, 1H), 8.17-8.14 (m, 1H), 7.75 (d, 1H), 7.34-7.29 (m, 1H), 6.62 (d, 1H).
Reaction SMILES: C1CCC(N=C=NC2CCCCC2)CC1.[NH2:16][CH2:17][C:18]([OH:20])=[O:19].O[C:22]1[C:31]([F:32])=[C:29]([F:30])[C:27]([F:28])=[C:25]([F:26])[C:23]=1[F:24]>CN(C=O)C>[NH2:16][CH2:17][C:18]([O:20][C:22]1[C:23]([F:24])=[C:25]([F:26])[C:27]([F:28])=[C:29]([F:30])[C:31]=1[F:32])=[O:19]
Reactant: Oc1c(F)c(F)c(F)c(F)c1F
Reactant: NCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CN(C)C=O
Product: NCC(=O)Oc1c(F)c(F)c(F)c(F)c1F
Temperature: 25 °C
Reaction time: 15 h
Yield: 19.1 %

Procedure:
DCC (308 mg, 1.5 mmol) was added to a DMF solution (10 mL) of HABA-Gly-OH (299 mg, 1 mmol) and PfpOH (276 mg, 1.5 mmol) while ice cooling, and the reaction mixture was stirred at room temperature for 15 hours. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (0-5% acetone/CH2Cl2) to give HABA-Gly-OPfp (46 mg, 10%) as an orange powder. 1H NMR (CDCl3) δ 9.67 (brs, 1H), 9.02 (brt, 1H), 7.8-7.7 (m, 3H), 7.6-7.5 (m, 2H), 7.23 (d, J=9 Hz, 1H), 6.86 (d, J=9 Hz, 2H), 4.67 (d, J=5 Hz, 2H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]4[CH:30]=[C:29]5[C:24]([CH2:25][CH2:26][C:27](=[O:31])[NH:28]5)=[CH:23][CH:22]=4)[CH2:12][CH2:11]3)=[CH:7][CH:8]=[CH:9][C:2]1=2.N1C=CC=CC=1.[C:38](Cl)(=[O:50])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49].O>C(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]2[C:6]([N:10]3[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]4[CH:30]=[C:29]5[C:24]([CH2:25][CH2:26][C:27](=[O:31])[N:28]5[C:38](=[O:50])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])=[CH:23][CH:22]=4)[CH2:14][CH2:15]3)=[CH:7][CH:8]=[CH:9][C:2]1=2
Reactant: O=C1CCc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc2N1
Reactant: CCCCCCCCCCCC(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: O
Product: CCCCCCCCCCCC(=O)N1C(=O)CCc2ccc(OCCCCN3CCN(c4cccc5sccc45)CC3)cc21

Procedure:
To a solution of 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-3,4-dihydro-1H-quinolin-2-one (0.3 g) synthesized in the same manner as in WO2006/112464 (Example 11) in methylene chloride (10 ml) was added pyridine (0.11 ml), with stirring under ice-cooling, dodecanoylchloride (0.24 ml) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture and the mixture was extracted with methylene chloride, and dried over sodium sulfate. The solvent was evaporated under reduced to pressure and the residue was purified by silica gel column chromatography (ethyl acetate) to give 7-[4-(4-benzo[b]thiophen-4-ylpiperazin-1-yl)butoxy]-1-dodecanoyl-3,4-dihydro-1H-quinolin-2-one (0.4 g).
Reaction SMILES: C[O:2][C:3](=[O:21])[CH2:4][C@@H:5]1[C:9]2=[CH:10][C:11]3[C:12]([CH:18]([CH3:20])[CH3:19])=[CH:13][C:14]([F:17])=[CH:15][C:16]=3[N:8]2[CH2:7][CH2:6]1.[CH:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]=1[C:32](Cl)=[O:33]>>[F:17][C:14]1[CH:13]=[C:12]([CH:18]([CH3:19])[CH3:20])[C:11]2[C:10]([C:32]([C:23]3[CH:24]=[CH:25][C:26]4[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:22]=3)=[O:33])=[C:9]3[C@@H:5]([CH2:4][C:3]([OH:2])=[O:21])[CH2:6][CH2:7][N:8]3[C:16]=2[CH:15]=1
Reactant: COC(=O)C[C@H]1CCn2c1cc1c(C(C)C)cc(F)cc12
Reactant: O=C(Cl)c1ccc2ccccc2c1
Product: CC(C)c1cc(F)cc2c1c(C(=O)c1ccc3ccccc3c1)c1n2CC[C@@H]1CC(=O)O

Procedure:
Starting from methyl[(1R)-6-fluoro-8-isopropyl-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl]acetate (Example 44A, Step 1) and 2-naphthoyl chloride, the title compound was synthesized following the procedures described in Step 1′ of Example 61 and Step 10 of Example 7.
Reaction SMILES: [Br:1][C:2]1[C:10]([N:11]([CH2:18][CH3:19])[CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:9][C:8]([Cl:20])=[CH:7][C:3]=1[C:4]([OH:6])=O.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[NH2:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[C:10]([N:11]([CH2:18][CH3:19])[CH:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:9][C:8]([Cl:20])=[CH:7][C:3]=1[C:4]([NH:63][CH2:64][C:65]1[C:66](=[O:73])[NH:67][C:68]([CH3:72])=[CH:69][C:70]=1[CH3:71])=[O:6]
Reactant: Cc1cc(C)c(CN)c(=O)[nH]1
Reactant: CCN(c1cc(Cl)cc(C(=O)O)c1Br)C1CCOCC1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCN(c1cc(Cl)cc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1Br)C1CCOCC1
Yield: 69.1 %

Procedure:
To a solution of 2-bromo-5-chloro-3-[ethyl(oxan-4-yl)amino]benzoic acid (109 mg, 0.3 mmol) in DMF (3 ml) at room temperature under nitrogen was added PyBOP (187 mg, 0.36 mmol) followed by N-ethyl-N-(propan-2-yl)propan-2-amine (78 μl, 0.45 mmol) and 3-(aminomethyl)-4,6-dimethyl-1,2-dihydropyridin-2-one (89%, 56 mg, 0.33 mmol). After stirring for 1 hour at room EtOAc (30 ml) was added to the reaction mixture and this was then washed with deionized water (2×10 ml) followed by saturated NaHCO3(aq) (2×10 ml). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified twice by FCC (5 g silica, Isolute cartridge, gradient of eluents; 100% DCM to 98:2 DCM:MeOH). The sample was dried in a vacuum oven for 18 hours to give 103 mg (65%) of the title compound as a pale yellow solid. LC-MS 94%, m/z=496.0/498.0/500.0, 1H NMR (500 MHz, Chloroform-d) δ 11.00 (s, 1H), 7.20-7.10 (m, 1H), 7.10-7.05 (m, 2H), 5.94 (s, 1H), 4.54 (d, J=5.9 Hz, 2H), 3.96 (d, J=11.4 Hz, 2H), 3.42-3.26 (m, 2H), 3.28-3.12 (m, 1H), 3.09 (q, J=7.0 Hz, 2H), 2.39 (s, 3H), 2.23 (s, 3H), 1.72 (td, J=8.5, 3.8 Hz, 4H), 0.90 (t, J=7.0 Hz, 3H).
Reaction SMILES: COC1C=CC([N:9](C(C2C=CC=CC=2)C2C=CC=CC=2)[C:10]2[C:11]3[CH:18]=[CH:17][N:16]([C@@H:19]4[O:34][C@H:33]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[C@@H:22]([O:23][C:24](=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C@@:20]4([CH3:44])[OH:21])[C:12]=3[N:13]=[CH:14][N:15]=2)=CC=1.CO.C(O)(=O)C>O>[NH2:9][C:10]1[C:11]2[CH:18]=[CH:17][N:16]([C@@H:19]3[O:34][C@H:33]([CH2:35][O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:38])[CH3:39])[C@@H:22]([O:23][C:24](=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C@@:20]3([CH3:44])[OH:21])[C:12]=2[N:13]=[CH:14][N:15]=1
Reactant: CCCCCCCC(=O)O[C@@H]1[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@@H](n2ccc3c(N(c4ccc(OC)cc4)C(c4ccccc4)c4ccccc4)ncnc32)[C@]1(C)O
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: CCCCCCCC(=O)O[C@@H]1[C@@H](CO[Si](C)(C)C(C)(C)C)O[C@@H](n2ccc3c(N)ncnc32)[C@]1(C)O

Procedure:
A solution of the compound from Step I (250 mg, 0.31 mmol) in 6:3:1 MeOH:acetic acid:H2O (10 mL) was stirred at 50° C. for 12 h. The reaction mixture was then concentrated to dryness. The residue was diluted with ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate solution (3×15 mL) and water (2×10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated. The crude product (200 mg) was used without further purification in Step K below. Further purification of a small amount was accomplished by silica gel column chromatography using 5% MeOH in CH2Cl2 as the eluent to give the title compound as a white foam.
Reaction SMILES: [C:1]1([S:7][CH:8]2[CH2:12][O:11][C:10](=[O:13])[O:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:14]OS([O-])=O.[K+].[OH2:20]>CO>[C:1]1([S:7]([CH:8]2[CH2:12][O:11][C:10](=[O:13])[O:9]2)(=[O:14])=[O:20])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1OCC(Sc2ccccc2)O1
Reactant: O=S([O-])OO
Reactant: O
Agent: [K+]
Solvent: CO
Product: O=C1OCC(S(=O)(=O)c2ccccc2)O1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
4-Phenylsulfanyl-[1,3]dioxolan-2-one) was dissolved in methanol, and OXONE® was added. The resulting mixture was agitated at room temperature for 5 minutes and water was added. The obtained reaction mixture was agitated at room temperature for 12 hours. From the agitated reaction mixture, methanol was removed using decompression distillation and the resulting product was extracted using methylene chloride. The extracted organic solvent layer was again extracted using water, moisture was removed using magnesium sulfate, and then organic solvent was removed using decompression distillation. Using silica gel chromatography, separation and purification were performed to obtain a pure target product, 4-benzenesulfonyl-[1,3]dioxolan-2-one.
Reaction SMILES: [C:1]([CH2:3][C:4]([C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12][CH3:13])=[O:11])=[CH:8][CH:7]=1)=[O:5])#[N:2].[H-].[Na+].[N:18]([C:21]1[CH:22]=[CH:23][C:24]2[O:28][C:27]([CH3:29])=[CH:26][C:25]=2[CH:30]=1)=[C:19]=S.[NH2:31][C@H:32]1[CH2:38][CH2:37][CH2:36][CH2:35][N:34]([CH2:39][C:40]([N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)=[O:41])[C:33]1=[O:47]>CN(C=O)C.C(OCC)(=O)C.[Hg](Cl)Cl>[CH3:13][O:12][C:10](=[O:11])[C:9]1[CH:14]=[CH:15][C:6]([C:4](=[O:5])[C:3]([C:1]#[N:2])=[C:19]([NH:31][C@H:32]2[CH2:38][CH2:37][CH2:36][CH2:35][N:34]([CH2:39][C:40](=[O:41])[N:42]3[CH2:43][CH2:44][CH2:45][CH2:46]3)[C:33]2=[O:47])[NH:18][C:21]2[CH:22]=[CH:23][C:24]3[O:28][C:27]([CH3:29])=[CH:26][C:25]=3[CH:30]=2)=[CH:7][CH:8]=1
Reactant: Cc1cc2cc(N=C=S)ccc2o1
Reactant: N[C@H]1CCCCN(CC(=O)N2CCCC2)C1=O
Reactant: COC(=O)c1ccc(C(=O)CC#N)cc1
Agent: Cl[Hg]Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C(=O)C(C#N)=C(Nc2ccc3oc(C)cc3c2)N[C@H]2CCCCN(CC(=O)N3CCCC3)C2=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 49.3 %

Procedure:
To a solution of methyl 4-(cyanoacetyl)benzoate (0.304 g, 1.50 mmol) in DMF (2 mL) was added sodium hydride (68.0 mg, 2.25 mmol). The reaction mixture was stirred at room temperature for 30 min. To the solution was then added 5-isothiocyanato-2-methylbenzofuran (0.284 g, 1.50 mmol). The reaction mixture was stirred at room temperature for 3 h at which time 1-[[(3S)-3-aminohexahydro-2-oxo-1H-azepin-1-yl]acetyl]pyrrolidine (0.358, 1.50 mmol) and mercury (II) chloride (0.407 g, 1.50 mmol) were added. The reaction mixture was stirred for another 30 min. The reaction mixture was passed through CELITE and diluted with 50 mL of ethyl acetate. The organic solution was washed 2×25 mL with brine and was concentrated in vacuo. The residue was purified by flash chromatography (silica, 4% methanol/ethyl acetate) to give the title compound as yellow solid (0.442 g, 49% yield): HPLC (method A) tR 4.1 min; MS (ESI, pos. ion spectrum) m/z 598 (M+H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][C:9]#[CH:10])([CH3:4])([CH3:3])[CH3:2].[CH3:12][O:13][C:14]([C:16]1[S:17][C:18](Br)=[CH:19][CH:20]=1)=[O:15]>C(#N)C.CCOC(C)=O.C(N(CC)CC)C>[CH3:12][O:13][C:14]([C:16]1[S:17][C:18]([C:10]#[C:9][CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:11])=[CH:19][CH:20]=1)=[O:15]
Reactant: COC(=O)c1ccc(Br)s1
Reactant: C#CCNC(=O)OC(C)(C)C
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(C#CCNC(=O)OC(C)(C)C)s1
Temperature: 25 °C
Yield: 63406.2 %

Procedure:
A mixture of prop-2-ynyl-carbamic acid tert-butyl ester (1.67 g, 0.011 mmol), 5-bromo-thiophene-2-carboxylic acid methyl ester (2.50 g, 0.011 mmol), tetrakistriphenylphosphine(0) palladium (0.622 g, 0.0538 mmol), Cul (0.102 g, 0.538 mmol) and triethylamine (1.57 mL, 0.011 mmol) in 50 mL acetonitrile under nitrogen was heated at reflux for 16 h. The reaction was cooled to room temperature, diluted with 75 mL EtOAc, washed with 5.5% HCl, water and brine, dried over MgSO4, filtered and concentrated in vacuo to an oil. The product was purified via flash chromatography (9:1 to 4:1 hexanes:EtOAc) to afford the title compound as an oil (2.06 g). MS 313 (M+18).
Reaction SMILES: O[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[CH:14]=2)=[CH:5][CH:4]=1.[Cl-].[Li+].CS([Cl:33])(=O)=O.C(OC(=O)C)C.Cl>ClCCl.C(N(CC)CC)C>[Cl:33][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])/[CH:11]=[CH:12]/[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)[CH:14]=2)=[CH:5][CH:4]=1
Reactant: CS(=O)(=O)Cl
Reactant: Cc1ccc(-c2cccc(/C=C/C(=O)Nc3ccc(CO)cc3)c2)cc1
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: Cc1ccc(-c2cccc(/C=C/C(=O)Nc3ccc(CCl)cc3)c2)cc1
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a mixture of (E)-N-[4-(hydroxymethyl)phenyl]-3-(4-methylphenyl)cinnamamide (3.00 g), lithium chloride (741 mg), triethylamine (3.06 ml), DMAP(catalytic amount) and dichloro-methane (300 ml) was added methanesulfonyl chloride (1.15 ml), and the mixture was stirred at room temperature for 13 hours. To the reaction mixture was added 4N hydrochloric acid ethyl acetate solution (3.3 ml), and the mixture was purified with column chromatography (ethyl acetate) and recrystallized from ethyl acetatediisopropylether to give (E)-N-[4-(chloromethyl)phenyl]-3-(4-methylphenyl)cinnamamide (2.00 g) as colorless crystals.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH:11]([C:32](=O)[NH:33][CH2:34][CH2:35][NH:36]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[NH:12]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:57]>CO>[ClH:57].[NH2:12][CH:11]([CH2:10][CH2:9][O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:32][NH:33][CH2:34][CH2:35][NH2:36]
Reactant: O=C(NCCNC(c1ccccc1)(c1ccccc1)c1ccccc1)C(CCOCc1ccccc1)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: Cl
Solvent: CO
Product: NCCNCC(N)CCOCc1ccccc1

Procedure:
2-(2-Benzyloxyethyl)-3-oxo-1,7-bis(triphenylmethyl) -1,4,7-triazaheptane is reacted in a manner analogous to the reaction of step (c) of Example 9 up to the point where the purified product is taken up in methanol and conc. hydrochloric acid is added. From this point the method described by M. Bessodes et al., Tetr. Lett., (1986) 579 to remove the triphenylmethyl protecting groups is employed: the product is taken up in a mixture of formic acid and diethylether and refluxed for several hours. After evaporation to dryness the product is dissolved in water, the pH is adjusted to 10 and the product is extracted with chloroform. The organic phase is evaporated and the product is taken up in dry ethanol. Dry hydrogen chloride gas is bubbled through the stirred solution cooled with an ice/water bath, and 1,5-diamino-1-(2-benzyloxy-ethyl)-3-azapentane hydrochloride is collected by filtration.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([F:18])[C:11]3[N:12]([C:14](I)=[CH:15][N:16]=3)[CH:13]=2)=[CH:4][CH:3]=1.[C:19]([C:21]1[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=1)#[CH:20]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([F:18])[C:11]3[N:12]([C:14]([C:20]#[C:19][C:21]4[CH:22]=[N:23][C:24]([NH2:27])=[N:25][CH:26]=4)=[CH:15][N:16]=3)[CH:13]=2)=[CH:4][CH:3]=1
Reactant: C#Cc1cnc(N)nc1
Reactant: Fc1cc(-c2ccc(Cl)cc2)cn2c(I)cnc12
Product: Nc1ncc(C#Cc2cnc3c(F)cc(-c4ccc(Cl)cc4)cn23)cn1

Procedure:
The title compound was prepared from 6-(4-chloro-phenyl)-8-fluoro-3-iodo-imidazo[1,2-a]pyridine (example C.30 step 2) (300 mg, 0.8 mmol) and 5-ethynyl-pyrimidin-2-ylamine (example D.2) (115 mg, 0.8 mmol) according to general procedure II. Obtained as an off-white solid (101 mg, 34%). MS (ISP) 364.1 [(M+H)+], 366 [(M+2+H)+]; mp 279-280° C.
Reaction SMILES: [NH:1]([CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].C([O:24][C:25]1[C:26](=[O:57])[C:27](=O)[C:28]=1[NH:29][C:30]1[CH:31]=[N:32][N:33]([CH3:55])[C:34]=1[NH:35][C:36]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)C.C(N(CC)CC)C.C(OCC)C>C(Cl)(Cl)Cl>[CH3:55][N:33]1[C:34]([NH:35][C:36]([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[C:30]([NH:29][C:28]2[C:25](=[O:24])[C:26](=[O:57])[C:27]=2[N:1]([CH2:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10])[CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH:31]=[N:32]1
Reactant: CCOc1c(Nc2cnn(C)c2NC(c2ccccc2)(c2ccccc2)c2ccccc2)c(=O)c1=O
Reactant: CC(C)(C)OC(=O)NCCNCCNC(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: Cn1ncc(Nc2c(N(CCNC(=O)OC(C)(C)C)CCNC(=O)OC(C)(C)C)c(=O)c2=O)c1NC(c1ccccc1)(c1ccccc1)c1ccccc1
Reaction time: 9 h
Yield: 62.6 %

Procedure:
To a solution of di-tert-butyl [iminobis(2,1-ethanediyl)]biscarbamate (2.13 g) and 3-ethoxy-4-{[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}-3-cyclobutene-1,2-dione (1.91 g) in chloroform (10 ml) was added triethylamine (0.558 ml), and the mixture was stirred under reflux. After 9 hours, additional di-tert-butyl [iminobis(2,1-ethanediyl)]biscarbamate (1.82 g) was added to the reaction mixture, and the mixture was stirred under reflux for 1 day. To the reaction mixture was added diethyl ether, and the solution was washed successively with 5% aqueous citric acid solution, water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel eluting with methylene chloride/methanol (20:1) to give di-tert-butyl {[(2-{[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}-3,4-dioxocyclobut-1-en-1-yl)imino]bis(2,1-ethanediyl)}biscarbamate (1.84 g) as a solid.
Reaction SMILES: [S:1](Cl)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[OH:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]2[CH:35]=[CH:34][C:33]([N:36]([CH3:38])[CH3:37])=[CH:32][CH:31]=2)=[CH:24][N:23]=1.O>N1C=CC=CC=1>[S:1]([O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]2[CH:35]=[CH:34][C:33]([N:36]([CH3:38])[CH3:37])=[CH:32][CH:31]=2)=[CH:24][N:23]=1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]
Reactant: CN(C)c1ccc(/C=C/c2ccc(OCCOCCOCCO)nc2)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCOCCOCCOc2ccc(/C=C/c3ccc(N(C)C)cc3)cn2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 40.9 %

Procedure:
Tosyl chloride (52 mg, 0.27 mmol) was added to a solution of compound 9 (43 mg, 0.116 mmol) in pyridine (5.0 ml) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then warmed up to room temperature and stirred for 3 h. Water was added and reaction mixture was extracted with ethyl acetate. Organic layer was separated, washed with brine, dried over sodium sulfate and evaporated. The residue was purified by PTLC (4% MeOH in DCM as developing solvent) to give product 10 (25 mg, Yield: 41%): 1H NMR (200 MHz, CDCl3): δ.8.14 (1H, d, J=2.0 Hz), 7.76 (3H, m), 7.39 (2H, d, J=8.8 Hz), 7.32 (2H, d, J=8.0 Hz), 6.87 (2H, m), 6.75 (3H, m), 4.46 (2H, t, J=4.6 Hz), 4.16 (2H, t, J=4.8 Hz), 3.81 (2H, t, J=4.8 Hz), 3.66 (6H, m), 2.99 (6H, s), 2.43 (3H, s), HRMS (EI) m/z calcd. for [C28H34N2O6S]+ 526.2138.
Reaction SMILES: [H-].[K+].[CH3:3][C:4]1([CH3:22])[O:8][CH:7]2[CH2:9][C:10]([CH3:21])([CH3:20])[C:11]([CH2:15][Si](C)(C)C)(O)[C:12]([CH3:13])=[C:6]2[O:5]1.O>O1CCCC1>[CH3:3][C:4]1([CH3:22])[O:8][CH:7]2[CH2:9][C:10]([CH3:21])([CH3:20])[C:11](=[CH2:15])[C:12]([CH3:13])=[C:6]2[O:5]1
Reactant: CC1=C2OC(C)(C)OC2CC(C)(C)C1(O)C[Si](C)(C)C
Agent: [H-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C=C1C(C)=C2OC(C)(C)OC2CC1(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 171.8 %

Procedure:
23 ml of a 20% suspension of potassium hydride in oil (containing about 3.7 g/92 mmol KH) were pipetted into a 500 ml round flask provided with a magnetic stirrer and dropping funnel having a fitted argon bubble counter and washed three times with 10 ml of hexane each time. Then, 120 ml of tetrahydrofuran were added thereto and a solution of 25.0 g (83 mmol) of 2,2,4,6,6-pentamethyl-5,6,7,7a-tetrahydro-5-trimethylsilylmethyl-1,3-benzodioxol-5-ol in 220 ml of tetrahydrofuran was added dropwise thereto at room temperature and the mixture was stirred at room temperature for 30 minutes (GC control: educt no longer present). Then, the mixture was cooled to 0° C. and 50 ml of water were slowly added dropwise. An analogous working up to that in (i) gave 29.7 g of crude 2,2,4,6,6-pentamethyl-5,6,7,7a-tetrahydro-5-methylidene-1,3-benzodioxol as a yellowish oil. A distillation on a very short Vigreux column gave at a boiling temperature of 50° C./0.02 mbar (2 Pa) 15.6 g (90% yield) of pure product as a colorless oil. 1H-NMR (CDCl3, 250 MHz): inter alia 1.12 and 1.23 (2s, in each case 3H, C(6)-(CH3)2), 1.50 and 1.53 (2s, in each case 3H, C(2)(CH3)2), 1.73 (s, 3H, C(4)-CH3), 4.55 (m, 1H, CH—O—), 4.79 (d, J=6 Hz, ═CH2); IR (film): 1693, 1112 cm−1; mass spectrum: 208 (M+, 40), 107(100);