Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][N:11]=[C:12]=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N+:14](=[C:16]1[N:20]=[CH:19][N:18]=[C:17]1[C:21]([NH2:23])=[O:22])=[N-:15]>CS(C)=O>[Si:1]([O:8][CH2:9][CH2:10][N:11]1[C:12](=[O:13])[N:20]2[CH:19]=[N:18][C:17]([C:21]([NH2:23])=[O:22])=[C:16]2[N:14]=[N:15]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCCN=C=O
Reactant: [N-]=[N+]=C1N=CN=C1C(N)=O
Solvent: CS(C)=O
Product: CC(C)(C)[Si](C)(C)OCCn1nnc2c(C(N)=O)ncn2c1=O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Crude 2-(tert-butyldimethylsilyloxy)ethyl isocyanate (422 mg, 2.097 mmol) was added drop wise to a solution of 5-diazoimidazole-4-carboxamide (250 mg, 1.823 mmol) in dimethylsulfoxide (2.5 mL) and the reaction mixture was stirred at room temperature. After 16 hours, the crude reaction mixture was applied to reverse phase silica (C18 silica) and eluted with water and then acetonitrile. The acetonitrile fractions were combined and purified by flash column chromatography (SiO2, gradient 0-100% acetonitrile in dichloromethane) to furnish the title compound as a white solid. Yield: 40 mg, 0.12 mmol, 6.5%. LCMS (ES+) m/z 339 (M+H)+ at 3.19 minutes. 1H NMR (400 MHz, d6-DMSO) δ: 8.87 (1H, s), 7.83 (1H, br s), 7.70 (1H, bs), 4.41 (2H, t), 3.98 (2H, t), 0.78 (9H, t), −0.03 (6H, s).
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[F:13][C:14]([F:43])([C:33]([F:42])([F:41])[C:34]([F:40])([F:39])[C:35]([F:38])([F:37])[F:36])[CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:21]=[N:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=2)=[N:24][CH:25]=1.[CH2:44](O)[CH2:45][CH2:46][CH2:47]/[CH:48]=[CH:49]/[CH2:50][CH2:51][CH2:52][CH3:53].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH2:44]([O:32][C:29]1[CH:28]=[CH:27][C:26]([C:23]2[N:22]=[CH:21][C:20]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][C:14]([F:13])([F:43])[C:33]([F:41])([F:42])[C:34]([F:39])([F:40])[C:35]([F:36])([F:37])[F:38])=[CH:25][N:24]=2)=[CH:31][CH:30]=1)[CH2:45][CH2:46][CH2:47]/[CH:48]=[CH:49]/[CH2:50][CH2:51][CH2:52][CH3:53]
Reactant: CCCC/C=C/CCCCO
Reactant: Oc1ccc(-c2ncc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cn2)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCC/C=C/CCCCOc1ccc(-c2ncc(OCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cn2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of DEAD (0.261 g, 1.50 mmol) in THF (20) was added dropwise to a stirred solution of 4-[5-(5,5,6,6,7,7,8,8,8-nonafluorooctyloxy)-pyrimidin-2-yl]-phenol (0.693 g, 1.50 mmol), trans-5-decen-1-ol (0.234 g, 1.50 mmol) and triphenylphosphine (0.399 g, 1.50 mmol) in THF (30) and the reaction mixture stirred at room temperature for 16 h. The solvent was removed in vacuo and the residues purified by column chromatography [silica gel, eluted with hexane/ethyl acetate (4:1)] to yield a colorless solid, which was recrystallized from ethanol.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:39][CH3:40])=[C:4]([N+:36]([O-])=O)[C:5]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])=[C:6]([C:8]2[C:9]3[CH:18]=[N:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=1.C(O)(=O)C>O1CCCC1.C(=O)(O)[O-].[Na+].C(OCC)(=O)C.[Fe]>[NH2:36][C:4]1[C:5]([O:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[F:35])=[C:6]([C:8]2[C:9]3[CH:18]=[N:17][N:16]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:24])([CH3:25])[CH3:26])[C:10]=3[C:11](=[O:15])[N:12]([CH3:14])[CH:13]=2)[CH:7]=[C:2]([Br:1])[C:3]=1[NH:39][CH3:40]
Reactant: CNc1c(Br)cc(-c2cn(C)c(=O)c3c2cnn3COCC[Si](C)(C)C)c(Oc2ccc(F)cc2F)c1[N+](=O)[O-]
Agent: [Fe]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CNc1c(Br)cc(-c2cn(C)c(=O)c3c2cnn3COCC[Si](C)(C)C)c(Oc2ccc(F)cc2F)c1N
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 52.3 %

Procedure:
A suspension of 4-[5-bromo-2-(2,4-difluorophenoxy)-4-(methylamino)-3-nitrophenyl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (0.209 g, 0.328 mmol) in tetrahydrofuran (1.38 mL) was treated with iron (0.183 g, 3.28 mmol), followed by the addition of acetic acid (1.38 mL, 24.3 mmol). The resultant reaction mixture was warmed to 60° C. and stirred at 60° C. for 1.5 h. The reaction mixture was treated with iron (0.0917 g, 1.64 mmol) and stirred at 60° C. for 14 h, after which time the reaction mixture was filtered through the pad of Celite and washed with ethyl acetate. The filtrate was concentrated in vacuo to give a crude residue. The crude residue was diluted with saturated solution of sodium bicarbonate and ethyl acetate. Layers were separated and the organic layer was washed with brine, dried with sodium sulfate, filtered, and concentrated in vacuo to give a crude residue. Purification by flash column chromatography (100% hexanes to 40% EtOAc/hexanes) gave the desired product (104 mg, 52%) as a white solid. LCMS calculated for C26H31BrF2N5O3Si (M+H)+: m/z=606.1, 608.1. found: 606.0, 608.0.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]1[OH:19])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(O)(=O)C.C(OCC)(=O)C>C(Cl)Cl.C1CCCCC1>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C:10]1=[O:19])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H]1Cc2ccccc2C[C@H]1O
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC1Cc2ccccc2CC1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.6 %

Procedure:
Under argon to a solution of trans 3 tert-butoxycarbonylamino 1,2,3,4-tetrahydro-2-naphthalenol (2.02 g) in methylene chloride (40 ml) was added pyridinium dichromate (4.3 g), molecular sieves 3A (6.3 g) and acetic acid (0.76 ml). After 1 hour stirring at room temperature the mixture was poured on a silica gel column (120 g, elution with ethyl acetate: cyclohexane, 1:3) to afford a crude material which was recrystallized from a diethyl ether/cyclohexane mixture to give the title compound (634 mg) as a white solid, m.p. 104-105° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([F:9])[CH:3]=1.[Br-].[N:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[Zn+].CCCCCC>C1COCC1.CCOC(C)=O.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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][N:11]=2)=[C:4]([F:9])[CH:3]=1
Reactant: [Zn+]c1ccccn1
Reactant: Fc1cc(Br)ccc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Fc1cc(Br)ccc1-c1ccccn1
Temperature: 70 °C
Yield: 47.8 %

Procedure:
1-Bromo-3-fluoro-4-iodo benzene (5.0 g, 16.6 mmol), 2-pyridylzinc bromide (7.4 g, 33.2 mmol) were combined in dry THF (100 mL) under argon and Pd(PPh3)4 (1.9 g, 1.6 mmol) was added. The reaction mixture was heated at 70° C. overnight. The reaction mixture was allowed to cool to ambient temperature. TLC analysis showed no starting material present. The reaction mixture was diluted with EtOAc (300 mL), and washed with H2O (3×100 mL), brine (300 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford a dark oil. The crude product was purified by column chromatography eluting with 1:9 EtOAc:Hexane to afford 2-(4-bromo-2-fluorophenyl)pyridine (2.0 g, 50% yield) as a yellow solid. MS 254.1 (M++H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH3:14])([CH3:13])[C:10](=[O:15])[CH:9]=2)=[CH:4][CH:3]=1.C1C(=O)N([Br:23])C(=O)C1>C(Cl)(Cl)Cl.C(Cl)Cl>[Br:23][C:9]1[C:10](=[O:15])[C:11]([CH3:13])([CH3:14])[O:12][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CC1(C)OC(c2ccc(Cl)cc2)=CC1=O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: CC1(C)OC(c2ccc(Cl)cc2)=C(Br)C1=O
Reaction time: 1 h
Yield: 51 %

Procedure:
To stirred solution of crude 5-(4-chlorophenyl)-2,2-dimethylfuran-3(2H)-one (2.1 g, 13.0 mmol) in CHCl3 (15 mL), NBS (3.93 g, 22.10 mmol) was added portionwise at RT. The reaction mixture was stirred for 1 h and then diluted with DCM (100 mL). The combined organic layers were washed with water (50 mL) and brine (30 mL), dried over Na2SO4, filtered, and then concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 4-bromo-5-(4-chlorophenyl)-2,2-dimethylfuran-3(2H)-one (2.0 g, 51% over three steps) as an off-white solid.
Reaction SMILES: [Br:1][CH:2]([CH2:6][CH2:7][Br:8])[C:3](Br)=[O:4].[C:9]([O:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[NH4+].[Cl-]>ClCCl>[Br:1][CH:2]([CH2:6][CH2:7][Br:8])[C:3]([NH:23][C:20]1[CH:19]=[CH:18][C:17]([NH:16][C:14]([O:13][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:15])=[CH:22][CH:21]=1)=[O:4]
Reactant: O=C(Br)C(Br)CCBr
Reactant: CC(C)(C)OC(=O)Nc1ccc(N)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)Nc1ccc(NC(=O)C(Br)CCBr)cc1
Reaction time: 0.17 h
Yield: 80.3 %

Procedure:
To the derivative 2,4-dibromobutyryl bromide (3.1 g) in dry dichloromethane (60 ml) pyridine (3.2 ml was added, the mixture was kept at 0° C. under a nitrogen atmosphere for 10 minutes and then the N-t-butoxy carbonyl-1,4 phenylene diamine (2.08 g) was dropped. After 1 hour the mixture was poured into a saturated solution of NH4Cl (200 ml) extracted with EA (3×150 ml) and the organic phase washed with brine (200 ml), dried and concentrated in vacuum, the crude was purified by flash chromatography (eluting with CH/EA 80:20) to give of the title compound as a yellow foam (3.5 g ). T.I.c. CH/EA 8:2, Rf=0.53.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.[N+:10]([C:13]1[CH:14]=[C:15]([S:19](Cl)(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1)([O-:12])=[O:11]>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][S:19]([C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([N+:10]([O-:12])=[O:11])[CH:14]=1)(=[O:20])=[O:21]
Reactant: COc1ccccc1N
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Product: COc1ccccc1NS(=O)(=O)c1cccc([N+](=O)[O-])c1
Yield: 89.5 %

Procedure:
Using o-anisidine (1.0 ml, 8.55 mmol) and 3-nitrobenzenesulfonyl chloride (1.95 g, 8.55 mmol), the procedure of Reference Example 2 was repeated to obtain 2.36 g (89.5%) of the title compound in the form of light yellow needle crystals.
Reaction SMILES: [C:1]1([S:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]3[NH:23][C:22](=O)[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:15]3=[O:25])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Br)(Br)([Br:28])=O>O>[Br:28][C:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:25])[N:14]([C:11]2[CH:12]=[CH:13][C:8]([S:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:9][CH:10]=2)[N:23]=1
Reactant: O=P(Br)(Br)Br
Reactant: O=c1[nH]n(-c2ccc(Sc3ccccc3)cc2)c(=O)c2ccccc12
Solvent: O
Product: O=c1c2ccccc2c(Br)nn1-c1ccc(Sc2ccccc2)cc1
Temperature: 25 °C
Yield: 84.2 %

Procedure:
2-(4-Phenylsulfanyl-phenyl)-2,3-dihydro-phthalazine-1,4-dione (0.10 g, 0.29 mmol) and phosphorus oxybromide (0.33 g, 12 mmol) were stirred at 150° C. for 40 min. H2O (50 ml) was added after cooling to room temperature. Extraction with dichloromethane, drying of the combined organic phases over Na2SO4, evaporation of the solvent and purification of the raw product by chromatography over silica gel with heptane:dichloromethane (2:1 to 0:1) gave the desired compound (0.10 g, 86%). 1H-NMR: (400 MHz, D6-DMSO) 8.36 (1H, d), 8.11 (1H, d), 8.00 (2H, m), 7.65 (2H, d), 7.44 (7H, m); MS (ESI+)=411.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1I)[CH:2]=[CH:3][CH3:4].C([O-])([O-])=O.[Na+].[Na+].CC([O-])=O.[Na+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:3]([C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[O:5][CH:1]=1)[CH3:4]
Reactant: CC=CCOc1ccccc1I
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCc1coc2ccccc12
Yield: 43 %

Procedure:
To a solution of 1-but-2-enyloxy-iodobenzene (7.60 g, 27.7 mmol) in DMF (46 mL) was added n-Bu4NCl (8.46 g, 30.4 mmol), Pd(OAc)2 (0.338 g, 1.30 mmol), Na2CO3 (6.01 g, 56.7 mmol) and NaOAc (2.77 g, 27.0 mmol). The mixture was heated to reflux under nitrogen atmosphere overnight. The mixture was diluted with EtOAc and washed with water. The combined organics were washed with brine and dried over Na2SO4. Purification by column chromatography (silica gel, hexanes) gave the title compound (1.74 g, 43%) as a yellow oil: 1H NMR (300 MHz, DMSO-d6) δ 7.75 (s, 1H), 7.63-7.61 (m, 1H), 7.55 (t, J=6.6 Hz, 1H), 7.34-7.23 (m, 2H), 2.71-2.63 (m, 2H), 1.28 (t, J=7.5 Hz, 3H); ESI MS m/z 147 (M+H)+.
Reaction SMILES: [CH3:1][NH:2][CH3:3].[CH3:4][O:5][C:6]1[CH:7]=[C:8]([S:12](Cl)(=[O:14])=[O:13])[CH:9]=[CH:10][CH:11]=1.N1C=CC=CC=1.O>C1COCC1>[CH3:4][O:5][C:6]1[CH:7]=[C:8]([S:12]([N:2]([CH3:3])[CH3:1])(=[O:14])=[O:13])[CH:9]=[CH:10][CH:11]=1
Reactant: CNC
Reactant: COc1cccc(S(=O)(=O)Cl)c1
Solvent: c1ccncc1
Solvent: O
Solvent: C1CCOC1
Product: COc1cccc(S(=O)(=O)N(C)C)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 76 %

Procedure:
Dimethylamine (40% in H2O, 1 mL) was added to a solution of 3-methoxybenzenesulfonyl chloride (0.50 g, 2.4 mmol) and pyridine (1 mL) in THF (5 mL). The reaction mixture was allowed to stir at rt for 48 h, then was poured into H2O and extracted with EtOAc. The organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to give an oil which was chromatographed (10-80% EtOAc in hexane) to give 0.400 g (76%) of the title compound. MS (ESI) 216 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[N:5]([C:32]1[CH:33]=[C:34](OS(C(F)(F)F)(=O)=O)[CH:35]=[CH:36][CH:37]=1)[C:6]([CH:12]([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]3[C:16]=1[N:17]=[CH:18][N:19]3[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[CH3:13])=[N:7]2.C(N(CC)CC)C.[CH3:54][Si:55]([C:58]#[CH:59])([CH3:57])[CH3:56]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:46])[N:5]([C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:59]#[C:58][Si:55]([CH3:57])([CH3:56])[CH3:54])[CH:33]=1)[C:6]([CH:12]([NH:14][C:15]1[N:23]=[CH:22][N:21]=[C:20]3[C:16]=1[N:17]=[CH:18][N:19]3[CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:29])([CH3:31])[CH3:30])[CH3:13])=[N:7]2
Reactant: C#C[Si](C)(C)C
Reactant: Cc1cccc2nc(C(C)Nc3ncnc4c3ncn4COCC[Si](C)(C)C)n(-c3cccc(OS(=O)(=O)C(F)(F)F)c3)c(=O)c12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cc1cccc2nc(C(C)Nc3ncnc4c3ncn4COCC[Si](C)(C)C)n(-c3cccc(C#C[Si](C)(C)C)c3)c(=O)c12
Temperature: 100 °C
Reaction time: 8 h
Yield: 63 %

Procedure:
A 5-mL reaction vial equipped with a magnetic stirrer was purged with nitrogen and charged with compound 138 (220 mg, 0.33 mmol), dichlorobis(triphenylphosphine)palladium(II) (27.1 mg, 0.039 mmol), and anhydrous DMF (1 mL). Triethylamine (146 mg, 1.44 mmol) and (trimethylsilyl)acetylene (102 mg, 1.04 mmol) were added, and the reaction mixture was stirred for 10 h at 90° C. and an additional 8 h at 100° C. Evaporation of the reaction mixture to dryness followed by column chromatography purification afforded 63% yield of compound 139 as an off-white solid. 1H NMR (CD3OΔ) δ (ppm) 7.43-8.33 (m, 8H), 7.30 (d, 1H, J=6.6 Hz), 5-0.64 (s, 2H), 5.14 (bs, 1H), 3.68 (t, 2H, J=8:0 Hz), 2.81 (s, 3H), 1.59-1.64 (m, 3H), 0.94 (m, 2H), 0.32 (s, 9H), −0.09 (s, 9H).
Reaction SMILES: [H-].[Na+].[CH2:3]([C:5]1[C:10]([CH:11]([C:13]2[C:14]([CH3:19])=[N:15][CH:16]=[N:17][CH:18]=2)[OH:12])=[CH:9][N:8]=[CH:7][N:6]=1)[CH3:4].[C:20](Cl)(=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22]>C1COCC1>[CH2:3]([C:5]1[C:10]([CH:11]([C:13]2[C:14]([CH3:19])=[N:15][CH:16]=[N:17][CH:18]=2)[O:12][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:9][N:8]=[CH:7][N:6]=1)[CH3:4]
Reactant: CC(C)(C)C(=O)Cl
Reactant: CCc1ncncc1C(O)c1cncnc1C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1ncncc1C(OC(=O)C(C)(C)C)c1cncnc1C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 86.5 %

Procedure:
To 3.2 mg of oil-free NaH was added 26 mg of 1-(4-ethylpyrimidin-5-yl)-1-(4-methylpyrimidin-5-yl)methanol in 1 ml THF at -30° C., followed by addition of 15 mg of pivaloyl chloride. After warming to room temperature and stirring for 1.5 hours, the reaction was quenched with 1 ml H2O and extracted with ether (3 times). The combined organics were washed with brine, dried (MgSO4) and evaporated to yield 30.7 mg of 1-(4-ethylpyrimidin-5-yl)-1-(4-methylpyrimidin-5-yl)-1-trimethylacetoxymethane as a yellow oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][C:14](=O)[C:13]=2[CH:12]=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+].C([BH3-])#[N:27].[Na+]>CO>[C:1]([O:5][C:6](=[O:20])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][CH:14]([NH2:27])[C:13]=2[CH:12]=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: [BH3-]C#N
Reactant: CC(C)(C)OC(=O)COc1cccc2c1CCCC2=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)COc1cccc2c1CCCC2N
Temperature: 25 °C
Reaction time: 4 h
Yield: 45.8 %

Procedure:
To a stirred solution of (5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (10.0 g, 36.2 mmol) in methanol (300 mL) was added ammonium acetate (55.0 g, 714 mmol) at room temperature under nitrogen. After being stirred for 4 hours at room temperature, the reaction mixture was cooled to 0° C. and sodium cyanoborohydride (5.7 g, 90 mmol) was added. The resulting mixture was allowed to warm to room temperature and stirred for an additional 48 hours. The reaction mixture was then concentrated under reduced pressure. To the residue was added saturated sodium carbonate solution to adjust the pH to about 7, and the resulting solution was extracted with ethyl acetate (500 mL×3). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Column chromatography (silica gel, 100-200 mesh, 2% to 5% methanol in dichloromethane) gave (5-amino-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (4.6 g, 46%) as a solid. MS cald. for C16H23NO3 277. obsd. 278 [(M+H)+].
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:7]=3[N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH2:23]([N:31]1[CH2:36][CH2:35][NH:34][C:33](=[O:37])[CH2:32]1)[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(Cl)Cl.CO.[NH4+].[OH-].[Cu]I>[CH3:11][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([N:34]3[CH2:35][CH2:36][N:31]([CH2:23][CH2:24][C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=4)[CH2:32][C:33]3=[O:37])[CH:10]=2)[C:6]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C:7]1=2
Reactant: O=C1CN(CCc2ccccc2)CCN1
Reactant: Cn1c2c(c3ccc(Br)cc31)CCN(C(=O)OC(C)(C)C)C2
Agent: [Cu]I
Agent: CN[C@@H]1CCCC[C@H]1NC
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CO
Product: Cn1c2c(c3ccc(N4CCN(CCc5ccccc5)CC4=O)cc31)CCN(C(=O)OC(C)(C)C)C2
Temperature: 110 °C
Reaction time: 16 h
Yield: 9.7 %

Procedure:
tert-Butyl 7-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (270 mg, 0.740 mmol), 4-phenethylpiperazin-2-one (150 mg, 0.735 mmol), CuI (140 mg, 0.735 mmol), trans-N,N′dimethylcyclohexane-1,2-diamine (104 mg, 0.735 mmol) and Cs2CO3 (311 mg, 0.956 mmol) in toluene (15 mL) were sparged with a nitrogen stream for 45 min and then stirred at 110° C. for 16 h. The mixture was diluted with 90:9:1 CH2Cl2/MeOH/NH4OH (50 mL) and washed with brine (3×50 mL). The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography eluting with methylene chloride and a 9:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 85% methylene chloride, to provide the title compound (35 mg, 10%) as a yellow oil: ESI MS m/z 489 [M+H]+.
Reaction SMILES: CO[C:3](=[O:26])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=3[F:25])=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[NH2:27][CH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1>>[F:25][C:19]1[C:20]([F:24])=[CH:21][CH:22]=[CH:23][C:18]=1[C:13]1[C:12]([CH2:11][O:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([NH:27][CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[O:26])=[CH:5][N:6]=2)=[C:16]([CH3:17])[O:15][N:14]=1
Reactant: NC1CCOCC1
Reactant: COC(=O)c1ccc(OCc2c(-c3cccc(F)c3F)noc2C)nc1
Product: Cc1onc(-c2cccc(F)c2F)c1COc1ccc(C(=O)NC2CCOCC2)cn1
Yield: 80 %

Procedure:
As described for example 261f, 6-[3-(2,3-difluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (200 mg, 0.56 mmol) was converted, using 4-aminotetrahydropyran instead of isopropylamine, to the title compound (190 mg, 80%) which was obtained as a white solid. MS: m/e=430.3 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][CH2:8][C:9]2=O)([O-:3])=[O:2].C(O)C.Cl.[NH2:19][OH:20]>O>[N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH2:6][CH2:7][CH2:8][C:9]2=[N:19][OH:20])([O-:3])=[O:2]
Reactant: NO
Reactant: O=C1CCCc2c1cccc2[N+](=O)[O-]
Agent: Cl
Solvent: CCO
Solvent: O
Product: O=[N+]([O-])c1cccc2c1CCCC2=NO
Yield: 90.3 %

Procedure:
In a 100 mL flask equipped with a reflux condenser were placed 2.26 g of 5-nitro-1-tetralone and 60 mL of ethanol. To the mixture was added a solution of hydroxylamine hydrochloride (1.82 g) in water (4.5 mL). The content of the flask was stirred with a stirring bar at reflux for 8 hours. After evaporating the solvent, the residue was purified by column chromatography (eluent: hexane/ethyl acetate=5/1)′ to give 2.2 g of 5-nitro-1-tetralone oxime.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH:11]2[O:16][CH2:15][C:14]([CH3:18])([CH3:17])[CH2:13][O:12]2)=[C:4]([OH:10])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.Cl[CH2:29][O:30][CH3:31]>C(Cl)Cl>[Br:1][C:2]1[C:3]([CH:11]2[O:12][CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][O:16]2)=[C:4]([O:10][CH2:29][O:30][CH3:31])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1
Reactant: COc1ccc(Br)c(C2OCC(C)(C)CO2)c1O
Reactant: COCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCOc1c(OC)ccc(Br)c1C1OCC(C)(C)CO1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To the solution of 3-bromo-2-(5,5-dimethyl-[1,3]dioxan-2-yl)-6-methoxy-phenol in DCM (20 mL) was added DIEA (697 μL, 4 mmol), followed by addition of chloromethoxymethane (228 μL, 3 mmol). After it was stirred at the room temperature for 72 h, the reaction mixture was evaporated and the residue was partitioned between NaHCO3 (50 mL) solution and EtOAc (40 mL). The aqueous layer was extracted with EtOAc (3×10 mL) and the combined extracts were washed with brine and dried through Na2SO4. Evaporation of solvent afforded the title compound. 1H NMR (CDCl3) δ 0.80 (s, 3H), 1.45 (s, 3H), 3.57 (s, 3H), 3.65 (d, J=12 Hz, 2H), 3.79 (s, 3H), 3.80 (d, J=12 Hz, 2H), 5.11 (s, 2H), 6.00 (s, 1H), 6.76 (d, J=8 Hz, 1H), 7.32 (d, J=8 Hz, 1H).