Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([SH:11])[C:5]=2[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-].[K+].[K+].[NH2:18][C:19]1[CH:24]=[C:23](F)[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][C:20]=1[NH:29][C:30](=[O:34])[CH:31]([CH3:33])[CH3:32]>CN(C=O)C>[NH2:18][C:19]1[CH:24]=[C:23]([S:11][C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:5]=2[CH:4]=[CH:3][N:2]=[CH:1]3)[C:22]([N+:26]([O-:28])=[O:27])=[CH:21][C:20]=1[NH:29][C:30](=[O:34])[CH:31]([CH3:32])[CH3:33]
Reactant: Sc1cccc2cnccc12
Reactant: CC(C)C(=O)Nc1cc([N+](=O)[O-])c(F)cc1N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)C(=O)Nc1cc([N+](=O)[O-])c(Sc2cccc3cnccc23)cc1N
Temperature: 100 °C
Reaction time: 1 h
Yield: 31 %

Procedure:
5-Isoquinolinethiol 500 mg (3.1 mmol) was dissolved in DMF 20 ml, potassium carbonate 1.29 g (9.3 mmol) and N1-(2-amino-4-fluoro-5-nitrophenyl)-2-methylpropane amide) 750 mg (3.1 mmol) were added, and the mixture was heated with stirring at 100° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, ether was added to the resulting residue to crystallize. The crystals were collected and washed with methanol to obtain N1-[2-amino-4-(5-isoquinolylsulfanyl)-5-nitrophenyl]-2-methylpropanamide 380 mg (31.0%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:48])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:44]([CH3:47])[CH2:45][CH3:46])[C@H:25]([O:42][CH3:43])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:40][CH3:41])[C@H:35]([C:37]([OH:39])=O)[CH3:36])=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[NH2:89][C@@H:90]([CH2:103][C:104]1[CH:109]=[CH:108][CH:107]=[CH:106][CH:105]=1)/[CH:91]=[CH:92]/[C:93]1[CH:98]=[CH:97][C:96]([S:99]([OH:102])(=[O:101])=[O:100])=[CH:95][CH:94]=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([CH3:48])[C@H:9]([C:13]([NH:15][C@H:16]([C:20]([N:22]([C@@H:24]([C@@H:44]([CH3:47])[CH2:45][CH3:46])[C@H:25]([O:42][CH3:43])[CH2:26][C:27]([N:29]1[CH2:33][CH2:32][CH2:31][C@H:30]1[C@H:34]([O:40][CH3:41])[C@@H:35]([CH3:36])[C:37](=[O:39])[NH:89][C@H:90](/[CH:91]=[CH:92]/[C:93]1[CH:94]=[CH:95][C:96]([S:99]([OH:102])(=[O:100])=[O:101])=[CH:97][CH:98]=1)[CH2:103][C:104]1[CH:105]=[CH:106][CH:107]=[CH:108][CH:109]=1)=[O:28])[CH3:23])=[O:21])[CH:17]([CH3:18])[CH3:19])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)O)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OC(C)(C)C)C(C)C
Reactant: N[C@H](/C=C/c1ccc(S(=O)(=O)O)cc1)Cc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](/C=C/c1ccc(S(=O)(=O)O)cc1)Cc1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OC(C)(C)C)C(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 90 mg (0.13 mmol) of N-(tert-butoxycarbonyl)-N-methyl-L-valyl-N-[(3R,4S,5S)-1-{(2S)-2-[(1R,2R)-2-carboxy-1-methoxypropyl]pyrrolidin-1-yl}-3-methoxy-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide in 4 ml of DMF were added 60 mg (0.16 mmol) of HATU and 69 μl of (0.39 mmol) HüNig's base. The reaction mixture was stirred at RT for 30 min and then admixed with 60 mg (0.15 mmol) 60.3 mg (0.13 mmol) of 4-[(1E,3S)-3-amino-4-phenylbut-1-en-1-yl]benzenesulphonic acid trifluoroacetate. After stirring overnight, the reaction mixture was purified by prep. HPLC. This gave 127 mg of a 44:56 mixture of the title compound and of the already deprotected amine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C:13](=[O:17])OCC)[C:6]([O:18][CH3:19])=[N:5]2.[N+:20]([C:23]1[CH:28]=[CH:27][C:26]([N:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:25][CH:24]=1)([O-:22])=[O:21]>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([NH:12][C:13]([N:32]1[CH2:33][CH2:34][N:29]([C:26]3[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:28][CH:27]=3)[CH2:30][CH2:31]1)=[O:17])[C:6]([O:18][CH3:19])=[N:5]2
Reactant: CCOC(=O)Nc1nc2ccc(F)cc2nc1OC
Reactant: O=[N+]([O-])c1ccc(N2CCNCC2)cc1
Product: COc1nc2cc(F)ccc2nc1NC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Yield: 89 %

Procedure:
Ethyl N-(6-fluoro-3-methoxyquinoxalin-2-yl)carbamate and 1-(4-nitrophenyl)piperazine were reacted by the same way with the example 85 to obtain the titled compound (yield, 89%). 1H NMR (200 MHz, DMSO-db): δ 3.57-3.59 (m, 4H), 3.64-3.66 (m, 4H), 4.04 (s, 3H), 7.05 (d, J=9.5 Hz, 2H), 7.44 (dt, J=8.9 and 2.9 Hz, 1H), 7.54 (dd, J=9.8 and 2.8 Hz, 1H), 7.81 (dd, J=9.1 and 5.9 Hz, 1H), 8.08 (d, J=9.4 Hz, 2H), 9.35 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][C:5]2[NH:6][C:7]([C:9](=O)[C:10]([F:13])([F:12])[F:11])=[N:8][C:4]=2[CH:3]=1.Cl.[NH2:19][OH:20].O>N1C=CC=CC=1.C(O)C>[Cl:1][C:2]1[C:16]([Cl:17])=[CH:15][C:5]2[NH:6][C:7]([C:9](=[N:19][OH:20])[C:10]([F:13])([F:12])[F:11])=[N:8][C:4]=2[CH:3]=1
Reactant: O=C(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F
Reactant: NO
Agent: Cl
Solvent: CCO
Solvent: O
Solvent: c1ccncc1
Product: ON=C(c1nc2cc(Cl)c(Cl)cc2[nH]1)C(F)(F)F
Temperature: 25 °C

Procedure:
1-(5,6-Dichloro-1H-benzoimidazol-2-yl)-2,2,2-trifluoro-ethanone (0.3005 g; 1.062 mmoles) and hydroxylamine hydrochloride (0.2389 g, 3.438 mmoles) were suspended in pyridine (3 mL) and ethanol (3 mL), then heated to 70° C. for 3 hrs. The reaction mixture was cooled to room temperature, water was water (50 mL) and the reaction mixture was then extracted with ethyl acetate (3×40 ml). The extracts were combined then washed with water (20 mL), brine (30 mL) and dried over Na2SO4. The filtrate was concentrated in vacuo and purified by column chromatography (SiO2; 30% ethyl acetate/CH2Cl2) to yield the title compound as an off-white solid, as a mixture of oxime E and Z isomers.
Reaction SMILES: CON(C)[C:4]([C:6]1[N:7]=[N:8][CH:9]=[CH:10][CH:11]=1)=[O:5].[CH3:13]OC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=S)=CC=1>C1(C)C=CC=CC=1>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([CH:4]([OH:5])[CH3:13])[N:7]=1
Reactant: CON(C)C(=O)c1cccnn1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CC(O)c1cccnn1
Temperature: 130 °C
Yield: 193.3 %

Procedure:
A suspension of compound 2 (180 mg, 0.4 mmol) and Lawesson's Reagent (180 mg, 0.44 mmol) in dry toluene (4 mL) was heated under 130° C. for 35 min in a CEM microwave reactor. The mixture was concentrated in vacuo and the residue was purified by column (eluent:petroleum ether:ethyl acetate=5:1) to give compound 3 as a white solid (96 mg, 50%) as a white solid.
Reaction SMILES: [CH:1]1[C:7]([F:8])=[C:6]([NH2:9])[NH:5][C:3](=[O:4])[N:2]=1.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH:18]=[C:19]([O:23][CH3:24])[C:20]=1[O:21][CH3:22])[C:15](Cl)=[O:16].O>N1C=CC=CC=1>[F:8][C:7]1[C:6]([NH:9][C:15](=[O:16])[C:14]2[CH:13]=[C:12]([O:11][CH3:10])[C:20]([O:21][CH3:22])=[C:19]([O:23][CH3:24])[CH:18]=2)=[N:5][C:3](=[O:4])[NH:2][CH:1]=1
Reactant: COc1cc(C(=O)Cl)cc(OC)c1OC
Reactant: Nc1[nH]c(=O)ncc1F
Solvent: c1ccncc1
Solvent: O
Product: COc1cc(C(=O)Nc2nc(=O)[nH]cc2F)cc(OC)c1OC
Yield: 90.4 %

Procedure:
To a suspension of 12.9 g of fluorocytosine in 78 ml of pyridine was added 23.1 g of 3,4,5-trimethoxybenzoyl chloride, and the mixture was reacted at 100° C. for 5 hours. After the completion of reaction, the reaction mixture was poured into 300 ml of water at room temperature with stirring. After stirring the resulting mixture for additional 3 hours, the precipitated crystals were collected by filtration, washed with water and then dried to obtain 29.2 g of 5-fluoro-N4 -(3,4,5-trimethoxybenzoyl)cytosine.
Reaction SMILES: C[O:2][C:3](=[O:32])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][NH:14][CH2:15][CH2:16][CH:17]2[CH2:21][CH2:20][N:19]([C:22]3[S:23][C:24]4[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:25]=4[N:26]=3)[CH2:18]2)[CH:6]=1.[OH-].[Na+].O1CCCC1>CO>[Cl:31][C:29]1[CH:28]=[CH:27][C:25]2[N:26]=[C:22]([N:19]3[CH2:20][CH2:21][CH:17]([CH2:16][CH2:15][NH:14][CH2:13][CH2:12][O:11][C:7]4[CH:6]=[C:5]([CH2:4][C:3]([OH:32])=[O:2])[CH:10]=[CH:9][CH:8]=4)[CH2:18]3)[S:23][C:24]=2[CH:30]=1
Reactant: COC(=O)Cc1cccc(OCCNCCC2CCN(c3nc4ccc(Cl)cc4s3)C2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)Cc1cccc(OCCNCCC2CCN(c3nc4ccc(Cl)cc4s3)C2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 13.3 %

Procedure:
A mixture of [3-[2-[[1-(6-chlorobenzothiazole-2-yl)pyrrolidine-3-yl]ethylamino]ethoxy]phenyl]acetic acid methyl ester (101 mg), 2N aqueous sodium hydroxide (0.535 mL), tetrahydrofuran (1 mL) and methanol (0.5 mL) was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over sodium sulphate. The solvent was evaporated under reduced pressure and the residue was washed with ethyl acetate/n-hexane to give the title compound (13 mg). Yield: 14%.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([O:24][CH:25]([F:27])[F:26])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2.[Cl:28]CCl>CN(C=O)C.Cl[Cu]>[Cl:28][C:2]1[CH:3]=[C:4]([O:24][CH:25]([F:27])[F:26])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2
Reactant: ClCCl
Reactant: O=C1c2c(I)cc(OC(F)F)cc2CN1Cc1ccc(OC(F)(F)F)cc1
Agent: Cl[Cu]
Solvent: CN(C)C=O
Product: O=C1c2c(Cl)cc(OC(F)F)cc2CN1Cc1ccc(OC(F)(F)F)cc1
Temperature: 140 °C
Reaction time: 1.5 h
Yield: 31 %

Procedure:
A solution of the 7-iodo-5-difluoromethoxy-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindolone (0.082 g, 0.16 mmol) in DMF (5 mL) was treated with CuCl (0.064 g, 0.65 mmol) and stirred at 140° C. for 1-2 h. After this time, the reaction mixture was diluted with dichloromethane (15 mL) and the solids removed by filtration. The filtrate was concentrated. Silica gel column chromatography using, typically 30% ethyl acetate in hexane, afforded 7-Chloro-2-(4-trifluoromethoxy-benzyl)-5-difluoromethoxy-2,3-dihydro-isoindolone (0.02 g, 31%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.08 (s, 2H), 4.58 (s, 2H), 6.37 (t, 1H), 6.87 (s, 1H), 7.01 (m, 3H), 7.17 (d, 2H). GC-MS: m/z 407 (M)+, 322 (M−85)+.
Reaction SMILES: [NH2:1][C:2]1[O:3][C:4]2[C:9]([CH:10]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([Br:24])[CH:15]=3)[C:11]=1[C:12]#[N:13])=[CH:8][CH:7]=[C:6]1[C:25]([OH:29])=[CH:26][CH:27]=[CH:28][C:5]=21.[C:30](=O)([O-])[O-].[K+].[K+].IC>C(#N)C.O>[NH2:1][C:2]1[O:3][C:4]2[C:9]([CH:10]([C:14]3[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([Br:24])[CH:15]=3)[C:11]=1[C:12]#[N:13])=[CH:8][CH:7]=[C:6]1[C:25]([O:29][CH3:30])=[CH:26][CH:27]=[CH:28][C:5]=21
Reactant: COc1cc(C2C(C#N)=C(N)Oc3c2ccc2c(O)cccc32)cc(Br)c1OC
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC#N
Solvent: O
Product: COc1cc(C2C(C#N)=C(N)Oc3c2ccc2c(OC)cccc32)cc(Br)c1OC
Reaction time: 1 h
Yield: 92 %

Procedure:
2-Amino-7-hydroxy-4-(3-bromo-4,5-dimethoxy-phenyl)-4H-benzo[h]chromene-3-carbonitrile (8) (45 mg, 0.1 mmol) and potassium carbonate (14 mg, 0.1 mmol) were taken in dry acetonitril (5 ml) at room temperature, stirred for 1 h, charged with iodomethane (15.6 mg, 0.11 mmol) and stirred further at room temperature under LC-MS control. The reaction mixture was diluted with water (10 ml) under stirring, stirred further at room temperature for 2 h, the precipitates were collected by filtration, washed with water and dried to get the title compound (43 mg, 92%).
Reaction SMILES: [C:1]([O:9]CC)(=[O:8])[CH2:2][C:3](OCC)=O.[H-].[Na+].ClC[C:16]1[CH:17]=[N:18][O:19][C:20]=1[C:21]1[S:22][C:23]([Cl:27])=[C:24]([Cl:26])[CH:25]=1.Cl>O1CCCC1.O>[Cl:26][C:24]1[CH:25]=[C:21]([C:20]2[O:19][N:18]=[CH:17][C:16]=2[CH2:3][CH2:2][C:1]([OH:9])=[O:8])[S:22][C:23]=1[Cl:27]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: ClCc1cnoc1-c1cc(Cl)c(Cl)s1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CCc1cnoc1-c1cc(Cl)c(Cl)s1
Reaction time: 0.17 h
Yield: 78.8 %

Procedure:
To a solution of diethyl malonate (3.55 g) in tetrahydrofuran (50 ml) was gradually added sodium hydride (60%, oil, 710 mg) at 0° C. The mixture was stirred for 10 min and a solution of 4-chloromethyl-5-(4,5-dichloro-2-thienyl)isoxazole (2.38 g) in tetrahydrofuran (50 ml) was added dropwise at 0° C. The mixture was stirred at room temperature for 15 hr. The reaction mixture was poured into water, acidified with 2N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was dissolved in a mixture of 6N hydrochloric acid (60 ml) and acetic acid (90 ml), and the solution was heated under reflux for 8 hr. The reaction mixture was concentrated, and water was added to the residue to give colorless crystals (2.04 g, yield 79%) of 3-[5-(4,5-dichloro-2-thienyl)-4-isoxazolyl]propionic acid. The crystals were recrystallized from ethyl acetate-hexane to give a colorless prism. melting point: 142–143° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:22])[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[N:13][C:12]=2[CH3:21])[CH:5]=[CH:6][C:7]=1[Cl:8].[Cl:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[F:33])[C:27](O)=[O:28]>>[Cl:8][C:7]1[CH:6]=[CH:5][C:4]([NH:9][C:10](=[O:22])[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[N:13][C:12]=2[CH3:21])=[CH:3][C:2]=1[NH:1][C:27](=[O:28])[C:26]1[CH:30]=[CH:31][C:32]([F:33])=[C:24]([Cl:23])[CH:25]=1
Reactant: Cc1nc(C(F)(F)F)ccc1C(=O)Nc1ccc(Cl)c(N)c1
Reactant: O=C(O)c1ccc(F)c(Cl)c1
Product: Cc1nc(C(F)(F)F)ccc1C(=O)Nc1ccc(Cl)c(NC(=O)c2ccc(F)c(Cl)c2)c1

Procedure:
N-(3-amino-4-chlorophenyl)-2-methyl-6-(trifluoromethyl)nicotinamide (0.15 mmol) was used in general procedure 2 with 3-chloro-4-fluorobenzoic acid (0.167 mmol). The product was purified by RP-HPLC to give N-(4-chloro-3-(3-chloro-4-fluorobenzamido)phenyl)-2-methyl-6-(trifluoromethyl)nicotinamide. MS (Q1) 486.1 (M)+
Reaction SMILES: [CH3:1][SiH2:2][O:3][Si:4]([CH3:7])([CH3:6])[CH3:5].[CH3:8][C:9](=C)[CH3:10].[C:12]1(C)C=CC=CC=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:8][CH:9]([CH3:10])[CH2:5][Si:4]([CH3:7])([CH3:6])[O:3][SiH:2]([CH3:12])[CH3:1]
Reactant: C[SiH2]O[Si](C)(C)C
Reactant: Cc1ccccc1
Reactant: C=C(C)C
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC(C)C[Si](C)(C)O[SiH](C)C
Temperature: 65 °C

Procedure:
An 80 mL Fischer-Porter high pressure bottle was charged with tetramethyldisiloxane (10.0 g), toluene (10.0 g) and Wilkinson's catalyst ((PPh3)3RhCl, 40 ppm), stirred and brought to 60° C. The bottle was attached to a manifold and pressurized with isobutylene (25 psig) and maintained at 60-70° C. for 8 h. The pressure was vented, and the reaction was sampled for GC analysis; found residual tetramethyldisiloxane, M′MR product and MRMR byproduct (2:95:3). The resulting material was stripped under vacuum (approx. 150 mm Hg) at 40° C. to remove olefin and M′M′, then filtered with Celite to yield 21.3 g M′MR product/toluene solution, 94% GC purity. This product was found to have an Si—H content of 11 cc H2/g by gasiometric titration.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2([OH:12])[CH2:11][CH2:10][CH2:9]2)=[CH:6][N:5]=[C:4]([C:13]#[N:14])[CH:3]=1.[F:15][C:16]([F:20])([F:19])[CH2:17][OH:18]>>[OH:12][C:8]1([C:7]2[C:2]([O:18][CH2:17][C:16]([F:20])([F:19])[F:15])=[CH:3][C:4]([C:13]#[N:14])=[N:5][CH:6]=2)[CH2:11][CH2:10][CH2:9]1
Reactant: OCC(F)(F)F
Reactant: N#Cc1cc(Cl)c(C2(O)CCC2)cn1
Product: N#Cc1cc(OCC(F)(F)F)c(C2(O)CCC2)cn1

Procedure:
The title compound was synthesized in analogy to Example 123c, using 4-chloro-5-(1-hydroxycyclobutyl)pyridine-2-carbonitrile (Example 126b) and 2,2,2-Trifluoro-ethanol (CAN 75-89-8) as starting material and isolated (609 mg, 71%); MS (ESI, m/z): 273.4 (M+H+).
Reaction SMILES: [F:1][CH:2]([F:18])[CH2:3][N:4]1[CH2:10][CH2:9][C:8]2[CH:11]=[C:12]([NH2:17])[C:13]([O:15][CH3:16])=[CH:14][C:7]=2[CH2:6][CH2:5]1.Cl[C:20]1[N:25]=[C:24]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[S:33]([CH:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])[C:23]([Cl:39])=[CH:22][N:21]=1>>[Cl:39][C:23]1[C:24]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[S:33]([CH:36]([CH3:38])[CH3:37])(=[O:35])=[O:34])=[N:25][C:20]([NH:17][C:12]2[C:13]([O:15][CH3:16])=[CH:14][C:7]3[CH2:6][CH2:5][N:4]([CH2:3][CH:2]([F:1])[F:18])[CH2:10][CH2:9][C:8]=3[CH:11]=2)=[N:21][CH:22]=1
Reactant: COc1cc2c(cc1N)CCN(CC(F)F)CC2
Reactant: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Product: COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CCN(CC(F)F)CC2

Procedure:
The title compound was prepared from 3-(2,2-Difluoro-ethyl)-8-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine and (2,5-Dichloro-pyrimidin-4-yl)-[2-(propane-2-sulfonyl)-phenyl]-amine in an analogous manner to Example 61e. Product isolated as an off-white foam (0.064 g, 65%). MP: 71-78° C. 1HNMR (400 MHz, CDCl3, δ, ppm): 9.50 (s, 1H), 8.55 (d, 1H, J=8.3 Hz), 8.16 (s, 1H), 7.99 (s, 1H), 7.95-7.91 (m, 1H), 7.63-7.57 (m, 1H), 7.50 (s, 1H), 7.29-7.23 (m, 1H), 6.65 (s, 1H), 5.91 (tt, 1H, J=56.1 Hz and 4.2 Hz), 3.87 (s, 3H), 3.26 (sept, 1H, J=6.9 Hz), 2.97-2.70 (m, 10H, 1.32 (d, 6H, J=7.1 Hz). MS: 566.49 (MH)+.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([CH3:9])[C:3]=1[NH2:4].C(=O)([O-])[O-].[K+].[K+].[N+:16]([C:19]1[CH:27]=[CH:26][C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=1)([O-:18])=[O:17]>O1CCCC1>[N+:16]([C:19]1[CH:20]=[CH:21][C:22]([C:23]([NH:4][C:3]2[C:5]([CH3:9])=[CH:6][CH:7]=[CH:8][C:2]=2[CH3:1])=[O:24])=[CH:26][CH:27]=1)([O-:18])=[O:17]
Reactant: Cc1cccc(C)c1N
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: Cc1cccc(C)c1NC(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C

Procedure:
A solution of 0.09 moles of 2,6-dimethyl-aniline in 35 ml of tetrahydrofuran was added to 200 ml of 20% (w/v) aqueous potassium carbonate contained in a one liter flask. A solution of 20 g of p-nitrobenzoyl chloride in 35 ml of tetrahydrofuran was added dropwise. The resulting mixture was refluxed for 12 hours while the pH was maintained at or above pH 8. The solution was cooled to room temperature and extracted three times, each with 100 ml of chloroform. The extracts were combined, dried over magnesium sulfate, and evaporated in vacuo. The resulting residue was crystallized from petroleum ether/benzene affording 15 g of the desired subtitle intermediate, m.p. 192-194.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[C:11]([N+:18]([O-])=O)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]3[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=3)=[O:35])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]2[N:15]=[C:40]([C:39]3[CH:38]=[CH:37][C:36]([C:34]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([N:24]5[CH2:23][CH2:22][O:21][CH2:26][CH2:25]5)=[CH:32][CH:31]=4)=[O:35])=[CH:43][CH:42]=3)[NH:18][C:11]=2[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1ccc(OCc2ccccc2)cc1[N+](=O)[O-]
Reactant: O=Cc1ccc(C(=O)Nc2ccc(N3CCOCC3)cc2)cc1
Product: O=C(Nc1ccc(N2CCOCC2)cc1)c1ccc(-c2nc3ccc(OCc4ccccc4)cc3[nH]2)cc1

Procedure:
Compound 639 was prepared according to the procedure similar to that described in Scheme III from 1-benzyloxy-3,4-dinitrobenzene and 4-(4-(4-morpholinophenyl)aminocarbonylbenzaldehyde. [M+H]+ calcd for C27H28N4O4: 473.21; found: 473.08.
Reaction SMILES: C([O:9][C:10]1[C:19]2[N:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]([C:20]([O:22][CH3:23])=[O:21])=[N:12][C:11]=1[C:24]([O:26][CH3:27])=[O:25])(=O)C1C=CC=CC=1.C(N)C1C=CC=CC=1.C(OCC)C>CO>[OH:9][C:10]1[C:19]2[N:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]([C:20]([O:22][CH3:23])=[O:21])=[N:12][C:11]=1[C:24]([O:26][CH3:27])=[O:25]
Reactant: COC(=O)c1nc(C(=O)OC)c2cccnc2c1OC(=O)c1ccccc1
Solvent: CO
Solvent: CCOCC
Solvent: NCc1ccccc1
Product: COC(=O)c1nc(C(=O)OC)c2cccnc2c1O
Temperature: 80 °C
Reaction time: 16 h

Procedure:
Dimethyl 8-(benzoyloxy)-1,6-naphthyridine-5,7-dicarboxylate (2.0 g, 5.46 mmol, prepared as in Example 164) was dissolved in dry methanol (4.0 ml) in a pressure tube. Benzylamine (0.58 g, 5.46 mmol) was added and the reaction capped and heated to 80 degrees C. under nitrogen for 16 hours. LCMS analysis indicated that the reaction was complete. The reaction was transferred to an Erlenmeyer flask and then diethyl ether was added to precipitate the product. Filtered and dried the solid in vacuo to obtain the desired compound.
Reaction SMILES: CO[C:3](=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1Cl.C([O-])([O-])=O.[Na+].[Na+].[CH3:21][NH:22][CH2:23][CH2:24][NH:25][CH3:26]>C(O)CCC.O>[CH3:21][N:22]1[C:5]2[C:6]([N+:10]([O-:12])=[O:11])=[CH:7][CH:8]=[CH:9][C:4]=2[C:3](=[O:14])[N:25]([CH3:26])[CH2:24][CH2:23]1
Reactant: CNCCNC
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCCCO
Solvent: O
Product: CN1CCN(C)c2c(cccc2[N+](=O)[O-])C1=O
Temperature: 80 °C
Yield: 59.7 %

Procedure:
2-Chloro-3-nitro-benzoic acid methyl ester (500 mg, 2.32 mmol) was dissolved in n-butanol (2.5 ml). Na2CO3 (246 mg, 2.32 mmol) was added followed by N,N′ dimethylethylenediamine (250 μL, 2.32 mmol). The reaction mixture was heated to 80° C. for 16 h. The reaction mixture was cooled and diluted with water (50 ml). The resulting mixture was extracted with EtOAc (3×50 mL), dried over MgSO4, and concentrated. Silica gel chromatography (0-100% EtOAc in hexanes) afforded 1,4-Dimethyl-9-nitro-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one as a yellow solid (326 mg, 60%). mp 146-147° C.; LCMS: m/z=236.23 (M+H+), 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J=8.1 Hz, 1.8 Hz, 1H), 7.77 (d, J=8.1 Hz, 1.8 Hz, 1H), 7.09 (dd, J=8.1 Hz, 1H), 3.54 (t, J=5.0 Hz, 2H), 3.42 (t, J=5.0 Hz, 2H), 3.22 (s, 3H), 2.71 (s, 3H).
Reaction SMILES: C([O:4][CH2:5][CH2:6][N:7]1[C:11]2=[CH:12][C:13]3[N:14]=[C:15]([C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([F:28])[CH:21]=4)[CH:16]=[N:17][C:18]=3[CH:19]=[C:10]2[CH:9]=[N:8]1)(=O)C.[Li+].[OH-].O>C1COCC1.CO.O>[OH:4][CH2:5][CH2:6][N:7]1[C:11]2=[CH:12][C:13]3[N:14]=[C:15]([C:20]4[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([F:28])[CH:21]=4)[CH:16]=[N:17][C:18]=3[CH:19]=[C:10]2[CH:9]=[N:8]1
Reactant: COc1ccc(-c2cnc3cc4cnn(CCOC(C)=O)c4cc3n2)cc1F
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(-c2cnc3cc4cnn(CCO)c4cc3n2)cc1F

Procedure:
To a mixture of 0.36 g of 1-(2-acetoxyethyl)-7-(3-fluoro-4-methoxyphenyl)-1H-pyrazolo[3,4-g]quinoxaline in 50 ml of THF:MeOH:H2O (3:1:1) is added 0.39 g of LiOH:H2O and the resulting mixture is stirred at room temperature overnight. The MeOH and THF are removed in vacuo and the yellow crystalline solid precipitates out from the aqueous solution. More water is added to the mixture and cooled in an ice-bath for 1/2 hour. The product is collected by filtration, washed with water and air dried. The product is recrystallized from ethylacetate, collected and air dried to obtain 1-[2-hydroxyethyl]-7-(3-fluoro-4-methoxyphenyl)-1H-pyrazolo[3,4-g]quinoxaline (m.p. 192°-195° C.).