Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[N:9]=[CH:10][C:5]2=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[N:3]=1.[N:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[C:23](B(O)O)[CH:22]=1>>[CH3:20][O:19][C:15]1[CH:14]=[C:13]([NH:12][C:4]2[N:3]=[C:2]([C:23]3[CH:22]=[N:21][C:30]4[C:25]([CH:24]=3)=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:7]=[C:6]3[N:8]([CH3:11])[N:9]=[CH:10][C:5]=23)[CH:18]=[CH:17][CH:16]=1
Reactant: OB(O)c1cnc2ccccc2c1
Reactant: COc1cccc(Nc2nc(Cl)nc3c2cnn3C)c1
Product: COc1cccc(Nc2nc(-c3cnc4ccccc4c3)nc3c2cnn3C)c1

Procedure:
6-Chloro-N-(3-methoxyphenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine 6 was reacted with quinoline-3-boronic acid using General Procedure A. Purification on silica yielded 117. NMR: (CDCl3): 3.90 (s, 3H, CH3), 4.17 (s, 3H, CH3), 6.90 (dd, H, ArH, J=2.4, 8.32), 7.20 (d, H, ArH, J=7.92), 7.35 (d, H, ArH, J=11.36), 7.41 (t, H, ArH, J=8.11), 7.51 (s, H, NH), 7.62 (t, H, ArH, J=7.51), 7.79 (t, H, ArH, J=6.970, 8.00 (d, H, ArH, J=8.12), 8.20 (d, H, ArH, J=8.43), 9.30 (d, H, ArH, J=1.8), 10.07 (d, H, ArH, J=2.09). MS: (ESI+) MH+=383.23
Reaction SMILES: [Si:1]([O:8][C@H:9]([C@@:11]1([NH:31][C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[C:16](=[O:17])[C@@:15]2([CH2:18][OH:19])[C@H:13]([O:14]2)[C@@H:12]1[NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH3:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CCN(CC)CC.[CH3:44][C:45]([Si:48](Cl)([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([CH3:47])[CH3:46].[NH4+].[Cl-]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:1]([O:8][C@H:9]([C@@:11]1([NH:31][C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[C:16](=[O:17])[C@@:15]2([CH2:18][O:19][Si:48]([C:45]([CH3:47])([CH3:46])[CH3:44])([C:55]3[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=3)[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C@H:13]([O:14]2)[C@@H:12]1[NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH3:10])([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: C[C@H](O[Si](C)(C)C(C)(C)C)[C@@]1(NC(=O)N(C)C)C(=O)[C@]2(CO)O[C@@H]2[C@@H]1NC(=O)OCc1ccccc1
Agent: CN(C)c1ccncc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@H](O[Si](C)(C)C(C)(C)C)[C@@]1(NC(=O)N(C)C)C(=O)[C@]2(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)O[C@@H]2[C@@H]1NC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 76.2 %

Procedure:
A flame-dried 25-mL round-bottomed flask was charged with alcohol 11 (1.0 g, 1.9 mmol, 1.0 equiv) and CH2Cl2 (9.5 mL). NEt3 (0.8 mL, 5.7 mmol, 3.0 equiv) and DMAP (0.023 g, 0.19 mmol, 0.1 equiv) were added and the solution was cooled 0° C. TBDPSCl (1.47 mL, 5.7 mmol, 3.0 equiv) was added dropwise and the reaction was warmed to rt and stirred for 8 h. Saturated NH4Cl(aq.) (10 mL) was added and the mixture was extracted with Et2O (3×15 mL). The combined organic extracts were washed with brine (10 mL), dried with magnesium sulfate, and concentrated in vacuo. The crude product was purified via flash chromatography (70:30 hexanes:EtOAc) to give the title compound as a pale yellow oil (1.1 g, 76%). Analytical data: [α]D19 −4.4 (c=0.70, CHCl3); 1H NMR (600 MHz, CDCl3): δ 7.67 (d, J=7.2 Hz, 2H), 7.62 (d, J=7.2 Hz, 2H), 7.44-7.30 (m, 11H), 5.68 (d, J=10.2 Hz, 1H), 5.23 (d, J=12.0 Hz, 1H), 4.97 (d, J=12.6 Hz, 1H), 4.74 (dd, J=3.0, 7.2 Hz, 1H), 4.70 (br s, 1H), 4.26 (d, J=12, 6 Hz, 1H), 4.11 (d, J=3.0 Hz, 1H), 4.03 (q, J=6.0 Hz, 1H), 3.92 (d, J=12.0 Hz, 1H), 2.68 (s, 6H), 1.19 (d, J=6.0 Hz, 3H), 1.01 (s, 9H), 0.92 (s, 9H), 0.13 (s, 6H); 13C NMR (150 MHz, CDCl3): δ 203.9, 156.8, 156.0, 136.7, 135.5, 135.4, 132.6, 132.3, 129.8, 129.7, 128.3, 128.1, 127.9, 127.8, 127.7, 74.1, 69.4, 66.4, 66.2, 60.8, 57.5, 52.2, 36.1, 26.6, 25.6, 19.1, 18.3, 17.8, −3.8, −4.8; LRMS (ESI+) Calcd. for C41H57N3O7Si2+H, 760.38. Found, 760.31. IR (thin film, cm−1) 3419, 2931, 2857, 2359, 1716, 1651, 1507, 1226, 1113, 828, 733; TLC (70:30 hexanes/EtOAc): Rf=0.30.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[NH2:37][C:38]1[CH:39]=[C:40]([CH:43]=[CH:44][C:45]=1[NH2:46])[C:41]#[N:42]>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][CH2:11][C:12](=[O:14])[NH:37][C:38]1[CH:39]=[C:40]([C:41]#[N:42])[CH:43]=[CH:44][C:45]=1[NH2:46])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NCCCC(=O)O
Reactant: N#Cc1ccc(N)c(N)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCC(=O)Nc1cc(C#N)ccc1N
Reaction time: 0.5 h
Yield: 65.7 %

Procedure:
A DMF solution (30 ml) containing 4-(t-butoxycarbonylamino)-butyric acid (1.53 g) was added with HOBt (1.07 g) and WSCI hydrochloride (1.51 g) and the whole was stirred for 0.5 hours. The reaction solution was dropped to a DMF solution (12 ml) containing the compound (1.00 g) obtained in Example 46-1. The whole was stirred at room temperature for 12 hours and then the solvent was distilled off. The resultant was dissolved in chloroform, washed with a saturated aqueous ammonium chloride solution and a saturated aqueous sodium hydrogen carbonate solution in the stated order, and dried with anhydrous magnesium sulfate. The residue obtained by distilling the solvent off was purified through silica gel column chromatography (ethyl acetate/chloroform), thereby obtaining the subject compound (1.57 g) as a milky-white solid.
Reaction SMILES: C[C:2]1[CH:3]=[C:4]([N:9]2[C:18](/[CH:19]=[CH:20]/[C@H:21]3[O:26][C:25](=[O:27])[CH2:24][C@H:23]([OH:28])[CH2:22]3)=[C:17]([CH:29]([CH3:31])[CH3:30])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:32])[CH:5]=[C:6](C)[CH:7]=1.C(Cl)[Cl:34]>>[Cl:34][C:7]1[CH:2]=[CH:3][C:4]([N:9]2[C:18](/[CH:19]=[CH:20]/[C@H:21]3[O:26][CH:25]([OH:27])[CH2:24][C@H:23]([OH:28])[CH2:22]3)=[C:17]([CH:29]([CH3:30])[CH3:31])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:32])=[CH:5][CH:6]=1
Reactant: Cc1cc(C)cc(-n2c(/C=C/[C@@H]3C[C@@H](O)CC(=O)O3)c(C(C)C)c3ccccc3c2=O)c1
Reactant: ClCCl
Product: CC(C)c1c(/C=C/[C@@H]2C[C@@H](O)CC(O)O2)n(-c2ccc(Cl)cc2)c(=O)c2ccccc12

Procedure:
(4R,6S)-(E)-6-(2-(2-(3,5-dimethylphenyl)-4-isopropyl-1-oxo-1,2-dihydroisoquinolin-3-yl)ethen-1-yl)-4-hydroxy-3,4,5,6-tetrahydro-2H-pyran-2-one, m.p.181°-185° C. [α]D =+30.8° C. (CH2Cl2 at 22° C.) Found: C,75.1; H,6.84; N,3.18%. Required: C,75.2; H,6.77; N,3.25%. [NMR in CDCl3, 1.38-1.55 (1H,m), 1.48 (6H,d,J=8 Hz), 1.59-1.68 (1H,m), 2.17 (1H,d,J=4 Hz), 2.32 (6H,s), 2.53 (2H,m), 3.53 (1H,sept,J=8 Hz), 4.01 (1H,m), 5.09 (1H,m), 5.59 (1H,dd,J=16 Hz and J=5 Hz), 6.11 (1H,dd,J=16 Hz and J=1.5 Hz), 6.78 (2H,s), 7.00 (1H,s), 7.49 (1H,m), 7.68 (1H,m), 8.02 (1H,d,J=8 Hz), 8.49 (1H,m)];
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([C:8]1[C:9]([Cl:15])=[C:10]([CH3:14])[CH:11]=[CH:12][CH:13]=1)=[O:7].[Br:16]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([C:8]1[C:9]([Cl:15])=[C:10]([CH2:14][Br:16])[CH:11]=[CH:12][CH:13]=1)=[O:7]
Reactant: Cc1cccc(C(=O)c2cccs2)c1Cl
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(c1cccs1)c1cccc(CBr)c1Cl

Procedure:
A mixture of 11.8 parts of 2-chloro-m-tolyl 2-thienyl ketone, 8.9 parts of N-bromosuccinimide, 100 parts of carbon tetrachloride and 0.25 parts of benzoyl peroxide is stirred and refluxed for 2 hours. The precipitated succinimide is filtered off and washed on the filter with carbon tetrachloride. The filtrate is dried and evaporated, yielding α-bromo-2-chloro-m-tolyl 2-thienyl ketone as a residue.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]([NH2:15])=O)=[CH:9]2)([O-:3])=[O:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:25])=CC=1>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13](=[S:25])[NH2:15])=[CH:9]2)([O-:3])=[O:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: NC(=O)c1cc2cccc([N+](=O)[O-])c2[nH]1
Solvent: C1CCOC1
Product: NC(=S)c1cc2cccc([N+](=O)[O-])c2[nH]1
Temperature: 50 °C
Reaction time: 8 h
Yield: 77.2 %

Procedure:
A mixture of 7-nitro-1H-indole-2-carboxamide (2.50 g), Lawesson's reagent (5.42 g) and tetrahydrofuran (50 mL) was stirred at 50° C. overnight. The reaction mixture was concentrated, and the resulting crystals were filtrated, washed with toluene, and dried to give the title compound (2.08 g, yield 77%) as yellow crystals. melting point>237° C. (decomposition).
Reaction SMILES: C(OC([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:23](=[O:24])[NH:22][C:21]3[C:16]2=[N:17][C:18]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)=[N:19][C:20]=3[C:25]([O:27]CC)=O)[CH2:11][CH2:10]1)=O)(C)(C)C.[NH2:37]C1C(C(OCC)=O)=NC(C2C=CC=C(O)C=2)=NC=1N[C@H]1CC[C@H](NC(OC(C)(C)C)=O)CC1>ClCCl>[NH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:23](=[O:24])[NH:22][C:21]3[C:16]2=[N:17][C:18]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=2)=[N:19][C:20]=3[C:25]([NH2:37])=[O:27])[CH2:11][CH2:10]1
Reactant: CCOC(=O)c1nc(-c2cccc(O)c2)nc(N[C@H]2CC[C@H](NC(=O)OC(C)(C)C)CC2)c1N
Reactant: CCOC(=O)c1nc(-c2cccc(O)c2)nc2c1[nH]c(=O)n2[C@H]1CC[C@H](NC(=O)OC(C)(C)C)CC1
Solvent: ClCCl
Product: NC(=O)c1nc(-c2cccc(O)c2)nc2c1[nH]c(=O)n2[C@H]1CC[C@H](N)CC1

Procedure:
Ethyl 9-(trans-4-(tert-butoxycarbonylamino)cyclohexyl)-2-(3-hydroxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxylate. Ethyl 5-amino-6-(trans-4-(tert-butoxycarbonylamino)cyclohexylamino)-2-(3-hydroxyphenyl)pyrimidine-4-carboxylate (0.150 g, 0.317 mmol) and 1,1′-1,1′-carbonyldiimidazole (0.514 g, 3.17 mmol) in dichloromethane (10 mL) were reacted according to General Procedure F and purified via biotage chromatography (0 to 60% EtOAc in hexanes) to afford the title compound (0.070 g, 44%). MS (ESI) m/z 498[M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[OH:10].ClC1C=C(OC)C=CC=1[O-].[K+].Cl[C:23]1[C:32]([N+:33]([O-:35])=[O:34])=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][C:24]=1[N+:36]([O-:38])=[O:37]>C(O)C>[N+:33]([C:32]1[CH:31]=[C:26]([CH:25]=[C:24]([N+:36]([O-:38])=[O:37])[C:23]=1[O:10][C:3]1[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=1[Cl:1])[C:27]([O:29][CH3:30])=[O:28])([O-:35])=[O:34]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Reactant: COc1ccc(O)c(Cl)c1
Agent: COc1ccc([O-])c(Cl)c1
Agent: [K+]
Solvent: CCO
Product: COC(=O)c1cc([N+](=O)[O-])c(Oc2ccc(OC)cc2Cl)c([N+](=O)[O-])c1
Yield: 66 %

Procedure:
The dinitro precursor was prepared by reacting 2-chloro-4-methoxyphenol (Aldrich Chemical Co., Milwaukee, Wis.) as the potassium 2-chloro-4-methoxyphenolate with methyl 4-chloro-3,5-dinitrobenzoate, as described in Example 1.2.1. The methyl 3,5-dinitro-4-(2′-chloro-4′-methoxyphenoxy)benzoate product (66% yield) was crystallized from ethanol to give orange crystals. Melting point: 116-119° C.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][OH:5].[H-].[Na+].[Cl:8][C:9]1[S:13][C:12]([S:14]([NH:17][C:18]2[C:23](Br)=[N:22][C:21]([Br:25])=[CH:20][N:19]=2)(=[O:16])=[O:15])=[CH:11][CH:10]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>COCCOC.C(OCC)(=O)C>[Cl:8][C:9]1[S:13][C:12]([S:14]([NH:17][C:18]2[C:23]([O:5][CH2:4][CH2:3][O:2][CH3:1])=[N:22][C:21]([Br:25])=[CH:20][N:19]=2)(=[O:16])=[O:15])=[CH:11][CH:10]=1
Reactant: O=S(=O)(Nc1ncc(Br)nc1Br)c1ccc(Cl)s1
Reactant: COCCO
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COCCOc1nc(Br)cnc1NS(=O)(=O)c1ccc(Cl)s1
Reaction time: 0.17 h

Procedure:
2-Methoxyethanol (0.04 g) was added to a stirred suspension of sodium hydride (0.05 g of 60%) in 1,2-dimethoxyethane (5 mL). After 10 minutes, 5-chloro-N-(3,5-dibromo-2-pyrazinyl)-2-thiophenesulphonamide (0.2 g) was added. After 30 minutes, 5% aqueous citric acid and ethyl acetate were added. The organic layer was separated dried (MgSO4) and the solvent was evaporated. Chromatography on silica eluting with hexane/ethyl acetate gave the title compound.
Reaction SMILES: [CH:1]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([OH:19])[CH:10]=3)[C:5]=2[CH:4]=[CH:3][C:2]=1[OH:20].[O:21](S(C(F)(F)F)(=O)=O)[S:22]([C:25]([F:28])([F:27])[F:26])(=O)=[O:23].Cl>C(Cl)Cl.N1C=CC=CC=1>[F:26][C:25]([F:28])([F:27])[S:22]([O:20][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[C:11](=[CH:10][C:9]([O:19][S:22]([C:25]([F:26])([F:27])[F:28])(=[O:21])=[O:23])=[CH:8][CH:7]=3)[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:18]=2[CH:1]=1)(=[O:23])=[O:21]
Reactant: Oc1ccc2c3ccc(O)cc3c3ccccc3c2c1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=S(=O)(Oc1ccc2c3ccc(OS(=O)(=O)C(F)(F)F)cc3c3ccccc3c2c1)C(F)(F)F
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Triphenylene-2,7-diol (314 mg, 1.2 mmol) was dissolved in DCM (13 mL) and pyridine (1 mL). The solution was cooled to 0° C. and Tf2O (0.48 mL, 2.65 mmol) was added dropwise. After stirring for 2 h, the reaction mixture was poured into HCl (1N) and extracted with DCM. The organic layer was washed with brine, dried over MgSO4, and concentrated. Taken on crude.
Reaction SMILES: [C:1]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:4])[CH2:2][CH3:3].[Na].[F:12][C:13]([F:17])([F:16])[C:14]#[N:15]>COCCOC>[NH2:15]/[C:14](/[C:13]([F:17])([F:16])[F:12])=[C:5](/[C:1](=[O:4])[CH2:2][CH3:3])\[C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: N#CC(F)(F)F
Reactant: CCOC(=O)CC(=O)CC
Agent: [Na]
Solvent: COCCOC
Product: CCOC(=O)/C(C(=O)CC)=C(\N)C(F)(F)F

Procedure:
To a mechanically stirred solution of 287 g (1.99 mol) of ethyl propionylacetate in 500 ml of dry DME was added under nitrogen 8.6 g (0.348 mol) of freshly cut sodium. After all sodium had dissolved, 256 g (2.69 mol) of trifluoroacetonitrile was added over a 35 hour period. The reaction mixture was concentrated. The residue was washed with water and extracted into 500 ml of ether. The ether solution was dried and concentrated. The residue was kugelrohr distilled at 67 Pa. and then was redistilled at 67 Pa through a spinning band column. The first fraction (bp 40°-78° C.) was discarded. The next fraction (bp 79°-82° C.) was 151 g (31.6%) of product, nD25 1.4574.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)[O:7][CH2:8][CH:9]1[CH2:13][CH2:12][CH2:11][NH:10]1)([O-:3])=[O:2].C=O.[BH3-][C:24]#N.[Na+]>CC#N>[CH3:24][N:10]1[CH2:11][CH2:12][CH2:13][CH:9]1[CH2:8][O:7][C:6]1[CH:14]=[C:15]([C:17]([F:20])([F:18])[F:19])[CH:16]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1
Reactant: [BH3-]C#N
Reactant: O=[N+]([O-])c1cc(OCC2CCCN2)cc(C(F)(F)F)c1
Agent: C=O
Agent: [Na+]
Solvent: CC#N
Product: CN1CCCC1COc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
Reaction time: 0.25 h

Procedure:
2-(3-Nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine (6 mmol) was dissolved in CH3CN (20 ml) and formaldehyde (2.4 ml, 37% aqueous) was added. NaBH3CN (607 mg) was added, an exotherm was observed. The pH is monitored every 15 min and adjusted to ˜7 with ACOH. After 45 min, the mixture was concentrated in vacuo and the residue is dissolved in EtOAc, washed with 6 N NaOH, 1 N NaOH, and 2 N HCl (3×). The acid washings were combined, adjusted to ˜pH 10 with solid Na2CO3 and extracted with EtOAc (2×). The EtOAc fractions were combined, dried with Na2SO4, and purified with flash chromatography (SiO2, 95:5:0.5 CH2Cl2:MeOH:NH4OH) to afford 1-methyl-2-(3-nitro-5-trifluoromethyl-phenoxymethyl)-pyrrolidine.
Reaction SMILES: C(N(CC)CC)C.Cl[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][N:17]=2)[N:12]=[CH:11][C:10]=1[N+:19]([O-:21])=[O:20].[CH2:22]([O:24][CH:25]([O:30][CH2:31][CH3:32])[CH2:26][CH2:27][CH2:28][NH2:29])[CH3:23]>ClCCl.C(=O)(O)[O-].[Na+]>[CH2:31]([O:30][CH:25]([O:24][CH2:22][CH3:23])[CH2:26][CH2:27][CH2:28][NH:29][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][N:17]=2)[N:12]=[CH:11][C:10]=1[N+:19]([O-:21])=[O:20])[CH3:32]
Reactant: O=[N+]([O-])c1cnc2cccnc2c1Cl
Reactant: CCOC(CCCN)OCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(CCCNc1c([N+](=O)[O-])cnc2cccnc12)OCC
Temperature: 5 °C
Reaction time: 2 h
Yield: 101.8 %

Procedure:
Triethylamine (3.9 mL, 27.9 mmol, 1.2 eq) was added to a suspension of 4-chloro-3-nitro[1,5]naphthyridine (4.87 g, 23.3 mmol, 1.0 eq) in dichloromethane (100 mL). The resulting solution was cooled to 5° C. and 4,4-diethoxybutylamine (5.36 mL, 27.9 mmol, 1.2 eq) was added dropwise over a period of 5 minutes. The reaction mixture was allowed to stir at ambient temperature for 2 hours and then diluted with saturated aqueous sodium bicarbonate (100 mL). The phases were separated and the aqueous phase was extracted with dichloromethane (2×50 mL). The combined organics were dried over magnesium sulfate, filtered, and then concentrated under reduced pressure to provide 7.93 g of (4,4-diethoxybutyl)(3-nitro[1,5]naphthyridin-4-yl)-amine as a red solid.
Reaction SMILES: [C:1]([C:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C:5](=[CH:6][CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:22](=[O:30])SC2C=CC=CN=2)[CH:4]=1)#[N:2].[CH3:31][C:32]([NH2:39])([C:34]1[S:35][CH:36]=[CH:37][CH:38]=1)[CH3:33]>>[CH3:31][C:32]([NH:39][C:22]([C@H:12]1[CH2:11][CH2:10][C@H:9]2[C@H:8]3[C@H:17]([CH2:16][CH2:15][C@:13]12[CH3:14])[C@:18]1([CH3:21])[C:5]([CH:4]=[C:3]([C:1]#[N:2])[CH2:20][CH2:19]1)=[CH:6][CH2:7]3)=[O:30])([C:34]1[S:35][CH:36]=[CH:37][CH:38]=1)[CH3:33]
Reactant: CC(C)(N)c1cccs1
Reactant: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)Sc1ccccn1
Product: CC(C)(NC(=O)[C@H]1CC[C@H]2[C@@H]3CC=C4C=C(C#N)CC[C@]4(C)[C@H]3CC[C@]12C)c1cccs1
Yield: 88 %

Procedure:
Following a procedure similar to that described in Example 3(b), but using S-2-pyridyl 3-cyanoandrosta-3,5-diene-17β-thiocarboxylate [prepared as described in Example 3(a)] and 1-methyl-1-(2-thienyl)ethylamine (prepared as described in Preparation 11a) as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained in a yield of 88%.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1.[C:31]([NH:34][NH2:35])(=[O:33])[CH3:32]>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]([NH:35][NH:34][C:31](=[O:33])[CH3:32])=[O:12])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: CC(=O)NN
Agent: CCOC(=O)N1c2ccccc2C=CC1OCC
Solvent: ClCCl
Product: CC(=O)NNC(=O)CNC(=O)OC(C)(C)C
Reaction time: 0.25 h

Procedure:
Under N2 atmosphere, to a dichloromethane 10 mL solution of N-tert-butyloxycarbonyl-glycine (500 mg, 2.85 mmol) was added EEDQ (706 mg, 2.85 mmol). After stirring for 15 min, to it was added acethydrazide (260 mg, 3.51 mmol) and stirring continued at rt overnight. The precipitate was collected by suction filtration to give the title compound as white fluffy solid (496 mg).
Reaction SMILES: [Br:1][C:2]1[C:3]([CH2:8][OH:9])=[N:4][CH:5]=[CH:6][CH:7]=1.[I:10][C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=1O.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1C=CC=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([CH2:8][O:9][C:16]2[CH:15]=[C:14]([Cl:17])[CH:13]=[CH:12][C:11]=2[I:10])=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: OCc1ncccc1Br
Reactant: Oc1cc(Cl)ccc1I
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: c1ccccc1
Solvent: CCOC(C)=O
Product: Clc1ccc(I)c(OCc2ncccc2Br)c1
Temperature: 0 °C
Yield: 49.3 %

Procedure:
(3-Bromo-pyridin-2-yl)-methanol (3.4 g, 18 mmol), and 2-iodo-5-chlorophenol 4.5 g, 18 mmol), are dissolved in benzene (60 mL) and cooled to 0° C. To the solution is added tributylphosphine (15 mL, 90 mmol), and 1,1′-(azodicarbonyl) dipiperidine (ADDP) (6.6 g, 18 mmol) and the mixture is heated at 40° C. for 3 h. The reaction mixture is diluted with ethyl acetate, washed with saturated aqueous NH4Cl and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (Biotage® Si65M, 15% ethyl acetate/hexane) to yield 3.77 g (51%) of the title compound as a white solid. GCMS m/e 296, 298 [M-I]−.
Reaction SMILES: CO[CH:3](OC)[CH2:4][NH:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:11][CH2:10]1)=[O:7].Cl>O.CO>[O:7]=[C:6]1[NH:5][CH:4]=[CH:3][N:8]1[CH:9]1[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[O:16])[CH2:13][CH2:14]1
Reactant: COC(CNC(=O)NC1CCN(C(=O)OCc2ccccc2)CC1)OC
Agent: Cl
Solvent: O
Solvent: CO
Product: O=C(OCc1ccccc1)N1CCC(n2cc[nH]c2=O)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 88.5 %

Procedure:
Benzyl 4-({[(2,2-dimethoxyethyl)amino]carbonyl}amino)piperidin-1-carboxylate (0.37 g) obtained in Example 16a) was dissolved in water (5 mL) and methanol (10 mL), and 1N hydrochloric acid (5 mL) was added thereto. The mixture was stirred at room temperature for 3 days. After the reaction mixture was concentrated under reduced pressure, the residue was diluted with water, and extracted with ethyl acetate. The extract was washed with water and saturated saline solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (0.27 g, 90%) as a colorless solid.
Reaction SMILES: [C:1]1([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(C1C=CC(C)=CC=1)(O[IH:30]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=O)(=O)=O.S(C1C=CC(C)=CC=1)([O-])(=O)=O.[F:56][Sb-:57]([F:62])([F:61])([F:60])([F:59])[F:58].[Na+]>CC(C)=O.C(O)(=O)C>[F:56][Sb-:57]([F:62])([F:61])([F:60])([F:59])[F:58].[CH2:8]([O:7][C:1]1[CH:6]=[CH:5][C:4]([I+:30][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[CH:3][CH:2]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: Cc1ccc(S(=O)(=O)O[IH](=O)c2ccccc2)cc1
Reactant: CCCCCCCCCCCCCCCCCCOc1ccccc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: F[Sb-](F)(F)(F)(F)F
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: CCCCCCCCCCCCCCCCCCOc1ccc([I+]c2ccccc2)cc1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
In accordance with the procedure of Example 1, octadecyl phenyl ether was prepared and a quantitative yield was obtained. There was added 50 ml of glacial acetic acid to a mixture of 196 grams (0.5 mol) of phenyliodoso tosylate and 173 grams (0.5 mols) of octadecyl phenyl ether dissolved in 200 ml dicholoromethane. After 1 hour stirring at 40° C., the reaction mixture was filtered then triturated with ether. A product, (4-octadecyloxyphenyl)phenyliodonium tosylate crystallized from solution and was recovered by filtration. There was obtained 340 grams (94.4% yield). The entire amount of the tosylate salt was dissolved in 1000 ml of hot acetone and 125 grams of sodium hexafluoroantimonate was added. The reaction mixture was stirred for 1 hour and the solution filtered to remove the sodium tosylate. The main filtrate was triturated with water and a white crystalline product (4-octadecyloxyphenyl)phenyliodonium hexafluoroantimonate was obtained. Recrystallization from ethanol/water gave the pure iodonium salt having a melting point of 94° C. and an 83 % yield. The acute oral toxicity of this photoinitiator was found to be greater than 5 g/kg. No toxic effects were observed during the 14 day test period and all the test animals (rats) gained weight during the test period.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20]Br)=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1.[CH3:22][NH:23][CH2:24][C:25]#[CH:26]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH2:18][CH2:19][CH2:20][N:23]([CH3:22])[CH2:24][C:25]#[CH:26])=[CH:16][C:11]=3[S:10][N:9]=2)=[CH:4][CH:3]=1
Reactant: C#CCNC
Reactant: BrCCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1
Product: C#CCN(C)CCCOc1ccc2c(-c3ccc(Br)cc3)nsc2c1

Procedure:
In analogy to example 3.1, 3-(4-Bromo-phenyl)-6-(3-bromo-propoxy)-benzo[d]isothiazole and Methyl-prop-2-ynyl-amine were converted to yield {3-[3-(4-Bromo-phenyl)-benzo[d]isothiazol-6-yloxy]-propyl}-methyl-prop-2-ynyl-amine as colorless oil, MS: 415 (MH+, 1Br).