Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([F:19])[CH:13]=2)=O)=[CH:4][CH:3]=1.Cl.[NH2:28][OH:29].C([O-])(O)=O.[Na+]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])[CH2:9][C:10]([C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([F:19])[CH:13]=2)=[N:28][OH:29])=[CH:4][CH:3]=1
Reactant: NO
Reactant: Cc1ccccc1C(CC(=O)c1cc(F)ncc1Cl)c1ccc(Br)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1ccccc1C(CC(=NO)c1cc(F)ncc1Cl)c1ccc(Br)cc1

Procedure:
In analogy to example 74, step 7, from 3-(4-bromo-phenyl)-1-(5-chloro-2-fluoro-pyridin-4-yl)-3-o-tolyl-propan-1-one and hydroxylamine hydrochloride in the presence of NaHCO3 was prepared the title compound as a mixture of E and Z isomers (1.6:1) as a white foam, MS (ESI−): m/z=445.0124 ([M−H]−, 1Br).
Reaction SMILES: [CH2:1]([C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([O:27]C(C)(C)C)=[O:26])=[CH:15][CH:14]=3)=[O:12])[N:6]2[CH:32]=1)[CH3:2].FC(F)(F)C(O)=O>>[CH2:1]([C:3]1[N:4]=[C:5]2[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([OH:27])=[O:26])=[CH:15][CH:14]=3)=[O:12])[N:6]2[CH:32]=1)[CH3:2]
Reactant: CCc1cn2c(C(=O)c3ccc(-c4ccccc4C(=O)OC(C)(C)C)cc3)cccc2n1
Solvent: O=C(O)C(F)(F)F
Product: CCc1cn2c(C(=O)c3ccc(-c4ccccc4C(=O)O)cc3)cccc2n1

Procedure:
Prepared analogously to Example 1c from 2-ethyl-5-[(2'-(tert.butyloxycarbonyl)biphenyl-4-yl)carbonyl]-imidazo[1,2-a]pyridine and trifluoroacetic acid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][CH3:15])[CH:5]=[CH:4][CH:3]=1.[F:16][C:17]([F:32])([F:31])[C:18]1[CH:19]=[C:20]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[C:21](Cl)=[O:22]>>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:15])[C:21](=[O:22])[C:20]2[CH:19]=[C:18]([C:17]([F:32])([F:31])[F:16])[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CNc1cnccc1-c1cccc(Cl)n1
Product: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnccc1-c1cccc(Cl)n1

Procedure:
The title compound was prepared in analogy to example 55, from (6-chloro-[2,4]bipyridinyl-3′-yl)-methyl-amine and 3,5-bis(trifluoromethyl)benzoyl chloride (CAS RN 1271-19-8) and using preparative HPLC for the purification. Off-white sticky solid (20%). MS (ESI): m/z=460.2 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH3:9])=[CH:4][N:3]=1.Br[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=1.C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-:19])=[O:18])[CH:12]=2)[C:5]([CH3:9])=[CH:4][N:3]=1
Reactant: Cc1cnc(Cl)nc1N
Reactant: O=[N+]([O-])c1cccc(Br)c1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1cnc(Cl)nc1Nc1cccc([N+](=O)[O-])c1

Procedure:
To a solution of 2-chloro-5-methylpyrimidin-4-amine (232 mg, 1.61 mmol) in 1,4-dioxane (40 mL) was added 1-bromo-3-nitrobenzene (359 mg, 1.78 mmol), Cs2CO3 (2.1 g, 6.4 mmol), Pd2(dba)3 (146 mg, 0.16 mmol), and 4,5-bis(diphenylphosphino)-9,9-dimethyxanthene (Xant Phos, 278 mg, 0.48 mmol). The mixture was heated under reflux for 4 h under Ar. The solid was filtered off and the filtrate washed with brine (1×100 mL). The organic solution was separated and dried (Na2SO4). The solvent was removed until 5 mL and hexane (100 mL) was added, the solid was collected by filtration. The crude product, the title intermediate 25, was used for next reaction without further purification.
Reaction SMILES: [CH:1]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:37])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:28])([CH3:27])[C:16](OS(C(F)(F)F)(=O)=O)=[CH:15][CH2:14]2)[CH2:11][CH2:10]3)([CH3:3])[CH3:2].[CH3:48][O:49][C:50]([C:52]1[CH:57]=[CH:56][C:55](B(O)O)=[CH:54][CH:53]=1)=[O:51].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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>[CH:1]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([C:38]([O:40][CH2:41][C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=2)=[O:39])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:37])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:27])([CH3:28])[C:16]([C:55]1[CH:56]=[CH:57][C:52]([C:50]([O:49][CH3:48])=[O:51])=[CH:53][CH:54]=1)=[CH:15][CH2:14]2)[CH2:11][CH2:10]3)([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc(B(O)O)cc1
Reactant: CC(C)[C@@H]1CC[C@]2(C(=O)OCc3ccccc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(OS(=O)(=O)C(F)(F)F)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C2=CC[C@]3(C)[C@H]4CC[C@@H]5[C@H]6[C@H](C(C)C)CC[C@]6(C(=O)OCc6ccccc6)CC[C@@]5(C)[C@]4(C)CC[C@H]3C2(C)C)cc1
Temperature: 90 °C
Yield: 88.9 %

Procedure:
A mixture of (1S,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 1-isopropyl-5a,5b,8,8,11a-pentamethyl-9-(trifluoromethylsulfonyloxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate (3.5 g, 5.16 mmol), 4-(methoxycarbonyl)phenylboronic acid (1.206 g, 6.70 mmol), Pd(Ph3P)4 (0.179 g, 0.155 mmol) and sodium carbonate (1.639 g, 15.47 mmol) in dioxane (20 mL) and water (20 mL) was heated up at 90° C. for 2 h. TLC indicated starting material was consumed and a new spot was present. The reaction mixture was purified by biotage with 0-10% ethyl acetate/hexanes to provide the title compound as white solid (3.05 g, 89%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.92 (d, J=8.24 Hz, 2H), 7.48-7.28 (m, 5H), 7.19 (d, J=7.93 Hz, 2H), 5.28 (dd, J=6.26, 1.68 Hz, 1H), 5.19-5.00 (m, 2H), 3.90 (s, 3H), 2.38-2.20 (m, 3H), 2.11 (dd, J=17.09, 6.41 Hz, 1H), 1.89-1.75 (m, 2H), 1.72-1.61 (m, 2H), 1.53-1.07 (m, 16H), 0.95 (s, 6H), 0.92 (s, 3H), 0.90 (s, 3H), 0.85 (d, J=6.71 Hz, 3H), 0.80 (s, 3H), 0.75 (d, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][N:21]=[C:22]4[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].O1CCCC1.CO.[OH-].[Li+:42]>O>[Li+:42].[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][N:21]=[C:22]4[CH2:27][CH2:28][C:29]([O-:31])=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]
Reactant: CCOC(=O)CCc1nccc2c(-c3noc(-c4ccc(OC(C)C)c(Cl)c4)n3)cccc12
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CC(C)Oc1ccc(-c2nc(-c3cccc4c(CCC(=O)[O-])nccc34)no2)cc1Cl
Temperature: 80 °C
Yield: 78.6 %

Procedure:
A round bottom flask was charged with ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoate (D8; 80 mg, 0.172 mmol), tetrahydrofuran (THF) (4.00 ml), methanol (4.00 ml), water (2 ml) and lithium hydroxide (4.11 mg, 0.172 mmol). The mixture was warmed to 80° C. for 2 h after which time the solvent was removed in vacuo and the resultant red solid triturated with diethyl ether. The resulting slurry was filtered and the solid dried in vacuo to give the title compound as a brick coloured solid (60 mg).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9]([OH:11])=O)=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:37]=[CH:36][C:16]2[CH2:17][CH2:18][C:19]3[C:20]([C:33]([NH2:35])=[O:34])=[N:21][N:22]([C:24]4[CH:32]=[CH:31][C:27]5[O:28][CH2:29][O:30][C:26]=5[CH:25]=4)[C:23]=3[C:15]=2[CH:14]=1>>[O:28]1[C:27]2[CH:31]=[CH:32][C:24]([N:22]3[C:23]4[C:15]5[CH:14]=[C:13]([NH:12][C:9]([C:3]6[C:2]([Cl:1])=[CH:7][CH:6]=[C:5]([Cl:8])[N:4]=6)=[O:11])[CH:37]=[CH:36][C:16]=5[CH2:17][CH2:18][C:19]=4[C:20]([C:33]([NH2:35])=[O:34])=[N:21]3)=[CH:25][C:26]=2[O:30][CH2:29]1
Reactant: O=C(O)c1nc(Cl)ccc1Cl
Reactant: NC(=O)c1nn(-c2ccc3c(c2)OCO3)c2c1CCc1ccc(N)cc1-2
Product: NC(=O)c1nn(-c2ccc3c(c2)OCO3)c2c1CCc1ccc(NC(=O)c3nc(Cl)ccc3Cl)cc1-2

Procedure:
The title compound was synthesized from 1.653 g of 3,6-dichloro-2-pyridine carboxylic acid (CP92740, prepared by the method of E. Marzi, A. Bigi, M. Schlosser, Eur. J. Org. Chem. 2001, 1371-1376) and the title compound of step 4 of Example 161 (2.0 g) by the same procedure used for Example 211. The title compound is a brown solid (2.4 g, 80%), m.p. 263-265° C. Its structure was confirmed by 1H NMR and LC/MS: 1H NMR (d6-DMSO): δ 2.82-3.01 (m, 4H)), 6.11 (s, 2H), 6.97-7.07 (m, 2H), 7.38 d, 1H, J=1 Hz), 7.81 (s, 1H), 7.33-7.42 (m, 3H), 7.52 (s, 1H), 7.51 (d, 1H, J=9 Hz), 8.15 (d, 1H, J=9 Hz), 10.57 (s, 1H). ESI mass spectrum for C25H18Cl2N5O4+: 522 (M+1).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]([O:14]C)=[O:13])=[N:10][CH:11]=1)[C:2]#[C:3][CH3:4].[OH-].[Li+].CCOC(C)=O.Cl>C1COCC1.O>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]([OH:14])=[O:13])=[N:10][CH:11]=1)[C:2]#[C:3][CH3:4]
Reactant: CC#CCOc1ccc(C(=O)OC)nc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CC#CCOc1ccc(C(=O)O)nc1
Reaction time: 72 h
Yield: 45.4 %

Procedure:
To a solution of methyl 5-(but-2-ynyloxy)picolinate (Intermediate 18, 1.42 g, 6.92 mmol) in THF (15 mL) was added lithium hydroxide (0.871 g, 20.76 mmol) dissolved in water (5 mL) to the reaction mixture at r.t. After 3 days of stirring was the reaction mixture partioned between water and EtOAc. The water was made acidic with aq. solution of HCl (2 M) and extracted with EtOAc. The organic phase was dried over MgSO4 and concentrated to give 0.60 g (45% yield) of the title compound: 1H NMR (500 MHz, CD3OD) δ ppm 1.84 (t, 3H), 4.87 (q, 2H), 7.57 (dd, 1H), 8.14 (d, 1H), 8.34 (d, 1H); MS (ES+) m/z 192 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]([O:16][C:17]2[C:22](C=C)=[CH:21][CH:20]=[CH:19][C:18]=2[O:25][CH3:26])[CH:14]=[CH2:15])(=[O:10])=[O:9])=[CH:4][CH:3]=1>ClCCl>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C@H:13]2[CH:14]=[CH:15][C:22]3[C:17](=[C:18]([O:25][CH3:26])[CH:19]=[CH:20][CH:21]=3)[O:16]2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: C=Cc1cccc(OC)c1O[C@H](C=C)COS(=O)(=O)c1ccc(C)cc1
Solvent: ClCCl
Product: COc1cccc2c1O[C@@H](COS(=O)(=O)c1ccc(C)cc1)C=C2
Temperature: 25 °C
Reaction time: 4 h
Yield: 89 %

Procedure:
To a solution of (2R)-2-(2-methoxy-6-vinylphenoxy)-3-butenyl 4-methyl-benzenesulfonate (3.00 g, 8.01 mmol) in dichloromethane (100 mL) was added bis(tricyclopentylphoshine)benzylidene ruthenium(IV) dichloride (0.59 g, 0.80 mmol) and the reaction mixture was stirred at room temperature for 4 h. The solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:3) provided 2.47 g (68%, >97% ee) of [(2R)-8-methoxy-2H-chromen-2-yl]methyl 4-methylbenzenesulfonate as a light purple oil. [α]D25=+150.31 (c 10.18 in chloroform, >97% ee); Rf=0.53 (silica, ethyl acetate:hexanes 2:3); Anal. Calcd. for C18H18O5S.0.2 H2O: C, 61.77; H, 5.29. Found: C, 61.49; H, 5.00.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[C:8]([OH:10])=[O:9].[CH3:11]O>>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[C:8]([O:10][CH3:11])=[O:9]
Reactant: N[C@H]1CCCC[C@H]1C(=O)O
Reactant: CO
Product: COC(=O)[C@@H]1CCCC[C@@H]1N
Reaction time: 1 h

Procedure:
cis-2-Amino-1-cyclohexane carboxylic acid (2500 mg, 17.5 mmol) was suspended in methanol (30 ml) at 0° C. Gaseous hydrochloric acid was bubbled through the suspension for 10 minutes. The reaction was allowed to reach room temperature then stirred under nitrogen for 1 h and the solvent removed under reduced pressure. The residue was azeotroped with diethyl ether (2×20 ml) and dried to give the title compound as a solid.
Reaction SMILES: [H-].[Na+].COC1C=CC(CO)=CC=1.[H][H].[C:15]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]([Br:37])[C:33](Br)([F:35])[F:34])(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O1CCCC1.C(OCC)C>[C:15]([O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([Br:37])=[C:33]([F:35])[F:34])(=[O:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: [H][H]
Reactant: O=C(OCCCCCCCCC(Br)C(F)(F)Br)c1ccccc1
Agent: COc1ccc(CO)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C(OCCCCCCCCC(Br)=C(F)F)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 35.5 %

Procedure:
Under a nitrogen atmosphere a stirred mixture of 0.09 gram (0.0036 mole) of sodium hydride in 10 ml of tetrahydrofuran was cooled in an ice bath, and 0.5 gram (0.0036 mole) of 4-methoxyphenylmethanol was added dropwise. When the evolution of hydrogen ceased, a solution of 1.5 grams (0.0033 mole) of 9,10-dibromo-10,10-difluorodecyl benzoate in 5 ml of tetrahydrofuran was added dropwise. Upon completion of addition, the reaction mixture was allowed to warm to ambient temperature where it stirred for 18 hours. After this time the reaction mixture was taken up in 150 ml of diethyl ether and was washed with 50 ml of water and then with 50 ml of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel. Elution was accomplished using methylene chloride. The appropriate fractions were combined and concentrated under reduced pressure yielding 0.44 gram of 9-bromo-10,10-difluoro-9-decenyl benzoate. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.Br[CH2:15][CH2:16][CH2:17]Br>>[CH2:12]([O:11][C:9]([C:8]1([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)[CH2:17][CH2:16][CH2:15]1)=[O:10])[CH3:13]
Reactant: BrCCCBr
Reactant: CCOC(=O)Cc1ccc(Br)cc1
Product: CCOC(=O)C1(c2ccc(Br)cc2)CCC1

Procedure:
Prepared according to the procedure described in Example 6, Step 1 using ethyl 4-bromophenylacetate and 1,3-dibromopropane.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([NH:16][C:17]2[CH:21]=[C:20]([CH3:22])[NH:19][N:18]=2)[N:3]=1>CC(O)C>[CH:9]([O:12][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([NH:16][C:17]2[CH:21]=[C:20]([CH3:22])[NH:19][N:18]=2)[N:3]=1)([CH3:10])[CH3:8]
Reactant: COc1cc2cc(Nc3cc(C)[nH]n3)nc(Cl)c2cc1OC
Solvent: CC(C)O
Product: COc1cc2cc(Nc3cc(C)[nH]n3)nc(OC(C)C)c2cc1OC

Procedure:
Similar procedure as described in example 10 was used, starting from propan-2-ol and (1-chloro-6,7-dimethoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine to give (1-isopropoxy-6,7-dimethoxy-isoquinolin-3-yl)-(5-methyl-1H-pyrazol-3-yl)-amine. LC-MS m/e 343(MH+).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:18]([OH:20])=[O:19])[CH2:13][CH2:14][CH2:15][CH2:16][NH2:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21](O)[CH3:22].S(=O)(=O)(O)O.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:13][CH2:14][CH2:15][CH2:16][NH2:17])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NCCCC[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: CCO
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Solvent: ClCCl
Product: CCOC(=O)[C@H](CCCCN)NC(=O)OCc1ccccc1
Yield: 91 %

Procedure:
A mixture containing 29.9 gm (0.017 mol) of Nα-benzyloxycarbonyl-L-lysine, 30 ml of ethanol, and 9.0 ml of concentrated sulfuric acid in 250 ml of methylene chloride was refluxed for 22.5 hours. The reaction mixture was then cooled to room temperature and basified to pH of about 13 by the careful addition of a saturated aqueous solution of potassium carbonate. The aqueous phase was removed and the organic phase was washed one more time with a saturated potassium carbonate solution. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo to give 29.8 gm (91% ) of ethyl Nα-benzyloxycarbonyl-L-lysinate (II-F) as an oil.
Reaction SMILES: [C:1]1([NH:7][C:8](=[O:12])OCC)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][CH2:14][CH:15]([NH2:17])[CH3:16]>>[CH3:16][CH:15]([NH2:17])[CH2:14][NH:13][C:8]([NH:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)=[O:12]
Reactant: CC(N)CN
Reactant: CCOC(=O)Nc1ccccc1
Product: CC(N)CNC(=O)Nc1ccccc1
Temperature: 125 °C

Procedure:
A mixture of ethyl phenylcarbamate (50 g.) and 1,2-diaminopropane (105 g.) is heated at 125° C. for 17 hours and cooled, and the excess of amine is removed by evaporation under reduced pressure. The residue is dissolved in ethyl acetate and the solution is washed with saturated brine, dried and evaporated to dryness. The residue is triturated with toluene and there is thus obtained as solid residue 1-methyl-2-(3-phenylureido)ethylamine, which is used without further purification.
Reaction SMILES: [Br:1][C:2]1[C:14]2[C:13]3[CH2:12][CH2:11][N:10]([C:15](=[O:24])[CH:16](Cl)[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH2:9][C:8]=3[CH:7]=[N:6][C:5]=2[NH:4][N:3]=1.CCN(C(C)C)C(C)C.[N:34]1([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1>O1CCOCC1>[Br:1][C:2]1[C:14]2[C:13]3[CH2:12][CH2:11][N:10]([C:15](=[O:24])[CH:16]([N:37]4[CH2:36][CH2:35][N:34]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:39][CH2:38]4)[C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[CH2:9][C:8]=3[CH:7]=[N:6][C:5]=2[NH:4][N:3]=1
Reactant: O=C(C(Cl)c1ccccc1)N1CCc2c(cnc3[nH]nc(Br)c23)C1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCN(C(C(=O)N2CCc3c(cnc4[nH]nc(Br)c34)C2)c2ccccc2)CC1
Temperature: 100 °C
Yield: 36 %

Procedure:
To a solution of 1-(1-bromo-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-chloro-2-phenylethanone (0.38 g, 0.94 mmol) in 1,4-dioxane (15 mL) was added Hunig's Base (0.50 mL, 2.82 mmol) and tert-butyl piperazine-1-carboxylate (0.349 g, 1.88 mmol). The reaction mixture was heated at 100° C. for 16 hours. The solvent was removed under reduced pressure and the crude product was purified using (SiO2, gradient from 80% EtOAc in hexanes to 100% EtOAc in hexane) to give the desired product, tert-butyl 4-(2-(1-bromo-8,9-dihydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-7(6H)-yl)-2-oxo-1-phenylethyl)piperazine-1-carboxylate as a white solid (0.188 g, 41%). M.p.=159-161° C.; 400 MHz 1H NMR (DMSO-d6) δ: 13.95 (s, 1H), 8.41 (s, 1H), 7.46-7.2 (m, 5H), 5.07-4.65 (m, 3H), 4.0-3.7 (m, 2H), 3.3-3.1 (m, 5H), 2.95-2.85 (m, 1H), 2.53-2.3 (m, 4H), 1.35 (s, 9H); LCMS [M+H]: 555.
Reaction SMILES: NN.[N+:3]([C:6]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([NH2:14])=[CH:8][C:7]=1[CH3:15])([O-])=O>[Ni].O>[CH3:13][O:12][C:10]1[CH:11]=[C:6]([NH2:3])[C:7]([CH3:15])=[CH:8][C:9]=1[NH2:14]
Reactant: COc1cc([N+](=O)[O-])c(C)cc1N
Agent: [Ni]
Agent: NN
Solvent: O
Product: COc1cc(N)c(C)cc1N

Procedure:
At a temperatutre of 80° C, hydrazine is allowed to act -- in the presence of Raney nickel -- on 18.2 parts by weight of 2-nitro-5-amino-4-methoxy-toluene in 100 parts by volume of water, until no nitro compound can be detected any more. The 2-methoxy-5-methyl-1,4-diaminobenzene having been formed is dissolved by an addition of hydrochloric acid up to a pH value of from 2 to 2.5. After filtering off from the Raney nickel, the diamine is monodiazotized at a temperature of from 0° to 5° C in the pH range of from 1.5 to 3.5 with a further addition of hydrochloric acid. Subsequently, the process is carried out according to the specifications of Example 6 and a disazo dyestuff of the formula (XIII) ##STR14## is obtained which dyes polyester fabric in an orange shade.
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].[Na+].[CH3:10][N:11]([C:13]([N:16]([CH3:18])[CH3:17])(Cl)[Cl:14])[CH3:12].C(OCC)C>C(#N)C>[F:1][C:2]([F:8])([F:7])[S:3]([O-:6])(=[O:5])=[O:4].[CH3:10][N:11]([C+:13]([N:16]([CH3:18])[CH3:17])[Cl:14])[CH3:12]
Reactant: CN(C)C(Cl)(Cl)N(C)C
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Na+]
Solvent: CC#N
Solvent: CCOCC
Product: CN(C)[C+](Cl)N(C)C
Reaction time: 1 h

Procedure:
2.01 g (11.7 mmol) of sodium trifluoromethanesulfonate in 20 ml of acetonitrile are added with stirring at room temperature to a solution of 2.0 g (11.7 mmol) of bis(dimethylamino)dichloromethane in 20 ml of acetonitrile. The mixture is stirred for one hour, and 40 ml of diethyl ether are added. After stirring for 12 hours, the solid NaCl is subsequently filtered off. The solvent is distilled off, and the crystals formed are dried under a reduced pressure of 10.0 Pa, giving 3.29 g of bis(dimethylamino)chlorocarbenium trifluoromethanesulfonate, corresponding to a yield of 98.8%.
Reaction SMILES: CO[C:3]([C:5]1[CH:10]=[C:9]([OH:11])[C:8]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:7][N:6]=1)=[O:4].[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>C(Cl)(Cl)Cl.CO>[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:3]([C:5]2[CH:10]=[C:9]([OH:11])[C:8]([O:12][CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:7][N:6]=2)=[O:4])[CH2:23][CH2:22]1
Reactant: COC(=O)c1cc(O)c(OCc2ccccc2)cn1
Reactant: CN1CCNCC1
Solvent: ClC(Cl)Cl
Solvent: CO
Product: CN1CCN(C(=O)c2cc(O)c(OCc3ccccc3)cn2)CC1
Temperature: 100 °C
Yield: 17.4 %

Procedure:
To a suspension of 2-methoxycarbonyl-4-hydroxy-5-benzyloxypyridine (18.15 g) in N-methylpiperazine (21.04 g) was heated to 100° C. for 3.5 hours. The resulting viscous solution was cooled to room temperature, diluted with a mixture of chloroform (270 ml) and methanol (30 ml) and subjected to column chromatography on silica gel (800 g). The eluate was evaporated in vacuo and the residue was purified by column chromatography on silica gel (600 g). The pure fractions were evaporated in vacuo and the residue was pulverized with diisopropyl ether to give 1-methyl-4-(4-hydroxy-5-benzyloxy-2-pyridylcarbonyl) piperazine (3.99 g).
Reaction SMILES: I[C:2]1[C:3]([CH3:12])=[N:4][C:5]2[N:6]([N:9]=[CH:10][N:11]=2)[C:7]=1[NH2:8].[C:13]([Si:15]([CH3:18])([CH3:17])[CH3:16])#[CH:14].C(N(CC)CC)C>C(#N)C.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.[Cu]I>[CH3:12][C:3]1[C:2]([C:14]#[C:13][Si:15]([CH3:18])([CH3:17])[CH3:16])=[C:7]([NH2:8])[N:6]2[N:9]=[CH:10][N:11]=[C:5]2[N:4]=1
Reactant: Cc1nc2ncnn2c(N)c1I
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1nc2ncnn2c(N)c1C#C[Si](C)(C)C
Yield: 50.1 %

Procedure:
A mixture of Example 4A (275 mg, 1.0 mmol), ethynyltrimethylsilane (283 μL, 2.6 mmol), bis(triphenylphosphine)palladium(II) dichloride (35 mg, 0.05 mmol), CuI (10 mg, 0.05 mmol), and triethylamine (279 μL, 2 mmol) in acetonitrile (4 mL) was heated at 90° C. under an atmosphere of nitrogen for 1 h. The resulting-mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuuo. The residue was purified by flash chromatograph on silica gel (eluting with ethyl acetate) to provide the title compound as a pale yellow solid (123 mg, 50% yield).