Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:3]([N:20]2[CH2:25][CH2:24][N:23](C(NC3C=CC=CC=3)=O)[CH2:22][CH2:21]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.Br[C:36]1C(N2CCN(CC)CC2)=C([N+]([O-])=O)C(N)=N[CH:41]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+].CN(C1C=CC(C=O)=CC=1)C>CN(C=O)C>[Br:1][C:2]1[C:3]([N:20]2[CH2:21][CH2:22][N:23]([CH2:36][CH3:41])[CH2:24][CH2:25]2)=[C:4]2[N:10]=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([N:17]([CH3:18])[CH3:19])=[CH:15][CH:16]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CCN1CCN(c2c(Br)cnc(N)c2[N+](=O)[O-])CC1
Reactant: CN(C)c1ccc(-c2nc3c(N4CCN(C(=O)Nc5ccccc5)CC4)c(Br)cnc3[nH]2)cc1
Agent: CN(C)c1ccc(C=O)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN1CCN(c2c(Br)cnc3[nH]c(-c4ccc(N(C)C)cc4)nc23)CC1
Reaction time: 18 h
Yield: 49 %

Procedure:
This was prepared using the same procedure as for 4-(6-bromo-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-N-phenylpiperazine-1-carboxamide, but here using 5-bromo-4-(4-ethylpiperazin-1-yl)-3-nitropyridin-2-amine (100 mg, 0.30 mmol), DMF (1.5 mL), 1M Na2S2O4 (3 eq, 0.90 mmol, 0.90 mL) and 4-(N,N-dimethylamino)benzaldehyde (1.05 eq, 0.32 mmol, 47 mg). After 18 h, filtration of the precipitate gave pure product (47 mg, 49%) as an off-white solid; 1H-NMR (500 MHz, DMSO-d6) 1.22 (br s, 3H, CH2CH3), 2.55 (s, 2H, CH2CH3), 2.73 (s, 2H, piperazine NCH2), 2.89 (s, 2H, piperazine NCH2), 3.01 (s, 6H, N(CH3)2), 3.80 (br s, 4H, piperazine N(CH2)2), 6.83 (d, J=8.9 Hz, 2H, N,N-dimethylaminophenyl), 8.02 (d, J=8.9 Hz, 2H, N,N-dimethylaminophenyl), 8.20 (s, 1H, imidazo[4,5-b]pyridine H-5), 13.23 (br s, 1H, imidazo[4,5-b]pyridine NH);
Reaction SMILES: B(Br)(Br)Br.[ClH:5].[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]2[N:13]([CH:25]([C:27]3[O:28][C:29](=[O:47])[C:30]4[C:35]([C:36]=3[C:37]3[CH2:38][C:39]([CH3:46])([CH3:45])[NH:40][C:41]([CH3:44])([CH3:43])[CH:42]=3)=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH3:26])[N:14]=[C:15]([C:16]3[CH:21]=[C:20]([O:22]C)[CH:19]=[C:18]([F:24])[CH:17]=3)[C:8]=12.CCO>C(Cl)Cl.C(O)=O.O.CC#N>[ClH:5].[NH2:6][C:7]1[N:12]=[CH:11][N:10]=[C:9]2[N:13]([CH:25]([C:27]3[O:28][C:29](=[O:47])[C:30]4[C:35]([C:36]=3[C:37]3[CH2:38][C:39]([CH3:46])([CH3:45])[NH:40][C:41]([CH3:44])([CH3:43])[CH:42]=3)=[CH:34][CH:33]=[CH:32][CH:31]=4)[CH3:26])[N:14]=[C:15]([C:16]3[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([F:24])[CH:17]=3)[C:8]=12
Reactant: COc1cc(F)cc(-c2nn(C(C)c3oc(=O)c4ccccc4c3C3=CC(C)(C)NC(C)(C)C3)c3ncnc(N)c23)c1
Agent: BrB(Br)Br
Agent: Cl
Solvent: O
Solvent: O=CO
Solvent: CC#N
Product: CC(c1oc(=O)c2ccccc2c1C1=CC(C)(C)NC(C)(C)C1)n1nc(-c2cc(O)cc(F)c2)c2c(N)ncnc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 76.1 %

Procedure:
1M Boron tribromide in DCM (2.1 ml, 2.100 mmol) was added to a solution of 3-(1-(4-amino-3-(3-fluoro-5-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride (226 mg, 0.373 mmol) in DCM (12 ml) and the resulting mixture was stirred at rt for 16 hrs. The suspension was slowly added at 0° C. to EtOH. The resulting mixture was concentrated under reduced pressure. Purification by RP-flash chromatography (Biotage 30 g C18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) yielded the title compound (168 mg, 0.284 mmol, 76% yield) as a pale yellow powder.
Reaction SMILES: CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.[Cl:19][C:20]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:21]=1[C:22]([OH:24])=O.[C:32]([NH:36][C:37](=[O:51])[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][N:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH:39]=1)([CH3:35])([CH3:34])[CH3:33].C(N(CC)CC)C>ClCCl>[C:32]([NH:36][C:37](=[O:51])[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][N:45]2[CH2:46][CH2:47][N:48]([C:22](=[O:24])[C:21]3[CH:25]=[CH:26][C:27]([N+:29]([O-:31])=[O:30])=[CH:28][C:20]=3[Cl:19])[CH2:49][CH2:50]2)[CH:39]=1)([CH3:35])([CH3:33])[CH3:34]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1Cl
Reactant: CC(C)(C)NC(=O)c1cccc(CN2CCNCC2)c1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1cccc(CN2CCN(C(=O)c3ccc([N+](=O)[O-])cc3Cl)CC2)c1
Yield: 91.6 %

Procedure:
1-Propanephosphonic acid cyclic anhydride (3.16 g, 92 mmol, 2.95 mL) was added dropwise to a solution of 2-chloro-4-nitrobenzoic acid (1 g, 4.9 mmol), N-tert-butyl-3-(piperazin-1-ylmethyl)benzamide (1.4169 g, 5.1 mmol) and triethylamine (1.4979 g, 14.7 mmol, 2 mL) in dichloromethane. The reaction was concentrated under reduced pressure and the residue was taken up in ethyl acetate, washed with water, sodium hydrogen carbonate and brine. The organic phase was concentrated under vacuum to afford the title compound (2.06 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2([C:27]3[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=3[F:34])[CH2:16][CH2:15][CH:14]([CH2:17][C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[OH:26])=[O:19])[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.Br[CH2:36][C:37]([O:39][CH3:40])=[O:38].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:40][O:39][C:37](=[O:38])[CH2:36][O:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:18](=[O:19])[CH2:17][CH:14]1[CH2:13][CH2:12][C:11]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:10])=[O:9])([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[CH:29][C:28]=2[F:34])[CH2:16][CH2:15]1
Reactant: COC(=O)CBr
Reactant: O=C(CC1CCC(c2cc(F)ccc2F)(S(=O)(=O)c2ccc(Cl)cc2)CC1)c1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccccc1C(=O)CC1CCC(c2cc(F)ccc2F)(S(=O)(=O)c2ccc(Cl)cc2)CC1
Temperature: 25 °C
Yield: 86.6 %

Procedure:
To a stirred solution of this phenol (100 mg, 0.20 mmol) in acetone (10 mL) under nitrogen was added methyl bromoacetate (21 μL, 0.22 mmol) and potassium carbonate (55 mg, 0.40 mmol). The mixture was heated to reflux for 14 h., cooled to room temperature, filtered and the filtrate evaporated to afford a residue (100 mg) which was purified using preparative thin layer chromatography eluting with diethyl ether:dichloromethane:iso-hexane 1:1:5 to give the desired product (25 mg).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[C:13]2[CH:14]=[CH:15][O:16][C:12]=2[CH:11]=[CH:10][CH:9]=1.[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O>[CH2:17]([O:7][C:8]1[C:13]2[CH:14]=[CH:15][O:16][C:12]=2[CH:11]=[CH:10][CH:9]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Oc1cccc2occc12
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: c1ccc(COc2cccc3occc23)cc1
Temperature: 2 °C
Reaction time: 0.83 h
Yield: 99 %

Procedure:
To a suspension of potassium carbonate (2.68 g, 19.4 mmol) in N,N-dimethylformamide (8 ml) was added a solution of 4-hydroxy-benzofuran (2.6 g, 19.4 mmol) in N,N-dimethylformamide (8 ml) at 2° C. under an argon atmosphere (for the preparation of 4-hydroxy-benzofuran see: G. Kneen, P. J. Maddocks, Syn. Commun. 1986, 16, 1635-1640.). After stirring for 50 min at 2° C., benzyl bromide (3.3 ml, 19.4 mmol) was added over a period of 15 min at 2° C. The suspension was stirred for additional 30 min at 2° C. and for 1.5 h at ambient temperature. After adding ice water (20 ml), the solution was extracted two times with diethyl ether. The combined extracts were washed three times with brine and dried over sodium sulfate. Evaporation of the solvent gave a yellow oil which was purified by column chromatography (silica gel, hexane) to give 4.3 g (19.2 mmol, 99%) of the title compound as colorless oil.
Reaction SMILES: [Li][CH2:2]CCC.[CH3:6][C:7]1([CH3:21])[CH2:12][O:11][CH:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:9][C@H:8]1[CH:19]=O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:21][C:7]1([CH3:6])[CH2:12][O:11][CH:10]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[O:9][C@H:8]1[CH:19]=[CH2:2]
Reactant: CC1(C)COC(c2ccccc2)O[C@H]1C=O
Reactant: [Li]CCCC
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: C1CCOC1
Product: C=C[C@@H]1OC(c2ccccc2)OCC1(C)C
Yield: 85.6 %

Procedure:
Following the general procedure for methylenation via Wittig-olefination of Description 8, a phosphorous ylide generated from 17.86 g (50.0 mmol) of methyltriphenylphosphonium bromide and 31.0 mmol of n-BuLi in 125 mL of anhydrous tetrahydrofuran (THF), was reacted with 5.5 g (25.0 mmol) of (4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-carbaldehyde (7b). Aqueous work-up followed by purification using column chromatography with mixtures of methyl tert-butyl ether (MTBE) and hexanes (Hxn) as eluent (MTBE/Hxn=9:1→MTBE/Hxn=6:1) provided 4.67 g (86% yield) of the title compound (7c) as a yellowish liquid. Rf=0.66 (MTBE/Hxn=1:6). 1H NMR (400 MHz, CHCl3): δ=0.82 (s, 3H), 1.16 (s, 3H), 3.67 (d, J=10.8 Hz, 1H), 3.78 (d, J=10.8 Hz, 1H), 4.05 (d, J=6.0 Hz, 1H), 5.24-528 (m, 1H), 5.31-5.37 (m, 1H), 5.55 (s, 1H), 5.87 (ddd, J=17.6, 10.4, 6.0 Hz, 1H), 7.30-7.40 (m, 3H), 7.52-7.55 (m, 2H) ppm. MS (ESI) m/z: 219.1 (M+H)+. The analytical data was consistent with that given in the literature (Ito, et al., Synthesis 1993, 137-140).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1.[NH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:22]([O:21][C:20](=[O:26])[NH:19][CH2:18][CH2:17][NH:16][CH:12]1[CH2:13][CH2:14][N:9]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])[CH2:10][CH2:11]1)([CH3:25])([CH3:23])[CH3:24]
Reactant: COc1ccccc1N1CCC(=O)CC1
Reactant: CC(C)(C)OC(=O)NCCN
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccccc1N1CCC(NCCNC(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 20 (186 mg, 0.906 mmol), 1 (153 mg, 0.955 mmol), and acetic acid (288 mg, 4.80 mmol) in methanol (1 mL) was treated with sodium cyanoborohydride (63 mg, 1.00 mmol) at room temperature. The resulting mixture was stirred at room temperature (2 h). The solvent was removed in vacuo and the residue dissolved in dichloromethane and sodium bicarbonate solution. The aqueous layer was extracted with two additional portions of dichloromethane and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 2 mm, 10% EtOH; 90% CHCl3) afforded the title compound (21).
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9]Br)=[CH:5][CH:4]=1.[CH3:11][C:12]1([CH3:21])[CH2:17][CH:16]([OH:18])[CH2:15][C:14]([CH3:20])([CH3:19])[NH:13]1>COCCOCCOC>[C:6]1([CH2:9][N:13]2[C:14]([CH3:19])([CH3:20])[CH2:15][CH:16]([OH:18])[CH2:17][C:12]2([CH3:21])[CH3:11])[CH:7]=[CH:8][C:3]([CH2:2][N:13]2[C:14]([CH3:20])([CH3:19])[CH2:15][CH:16]([OH:18])[CH2:17][C:12]2([CH3:21])[CH3:11])=[CH:4][CH:5]=1
Reactant: BrCc1ccc(CBr)cc1
Reactant: CC1(C)CC(O)CC(C)(C)N1
Solvent: COCCOCCOC
Product: CC1(C)CC(O)CC(C)(C)N1Cc1ccc(CN2C(C)(C)CC(O)CC2(C)C)cc1

Procedure:
In a 500 -milliliter, round-bottomed flask are placed 11.4 grams of α, α'-dibromo-p-xylene, 25.2 grams of 2, 2, 6, 6-tetramethyl-4-hydroxypiperidine and 120 milliliters of diglyme (dimethyl ether of diethylene glycol). The contents are refluxed for 19 hours with vigorous stirring and filtered hot. The diglyme from the filtrate is removed by distillation. The remaining solid is washed with methanol. The solid is then washed repeatedly with ether. The 1, 1'-(p-phenylenedimethylene) bis(2, 2, 6, 6-tetramethyl-4-piperidinol) is obtained as a white crystalline solid, is dried in a vacuum oven and has a melting point of 237°-239°C.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[NH:11]1[CH:15]=[CH:14][N:13]=[CH:12]1.C(=O)([O-])[O-].[K+].[K+]>[Cu]=O.N1C=CC=CC=1>[N:11]1([C:2]2[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=2)[CH:15]=[CH:14][N:13]=[CH:12]1
Reactant: CC(=O)c1cccc(Br)c1
Reactant: c1c[nH]cn1
Agent: O=[Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Product: CC(=O)c1cccc(-n2ccnc2)c1
Temperature: 25 °C
Yield: 15.4 %

Procedure:
A mixture of 25 g of 3'-bromoacetophenone, 9.0 g of imidazole, 18 g of anhydrous potassium carbonate, 1.0 g of copper oxide (CuO) and 30 ml of pyridine is refluxed for 64 hours. The mixture is cooled to room temperature, filtered and the filter cake washed with 50 ml of pyridine and 3×50 ml of dichloromethane. The combined filtrates are concentrated to dryness under vacuum. The residue is partitioned between 250 ml of dichloromethane and 150 ml of water. The emulsion is clarified by filtration through a pad of diatomaceous earth. The organic layer is separated, dried (MgSO4) and filtered through a pad of hydrous magnesium silicate. The pad is washed with 50 ml of dichloromethane and the combined filtrate is concentrated on a steam bath to 150 ml and while hot 300 ml of hexane is added. The mixture is cooled to room temperature, activated carbon added and the mixture filtered through diatomaceous earth. The filtrate is cooled to -10° C. and filtered to give 3.6 g of crystals, mp 69°-71° C. The filtrate is treated with activated carbon, filtered and the filtrate evaporated to give 12 g of crystals, mp 62°-65° C.
Reaction SMILES: FC(F)(F)C(O)=O.C(O[C:13](=[O:30])[C:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[C:24]([Cl:26])[N:23]=[C:22]([NH2:27])[N:21]=2)[C:17]([CH3:28])=[CH:16][C:15]=1[CH3:29])(C)(C)C.C(N(C(C)C)CC)(C)C.ON1C(=O)CCC1=O.Cl.C(N=C=NCCCN(C)C)C.[NH2:60][CH2:61][C:62]1([CH2:66][NH:67][C:68]([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[CH2:65][O:64][CH2:63]1.[Cl-].[Na+]>CN(C)C=O.ClCCl>[NH2:27][C:22]1[N:21]=[C:20]([C:18]2[C:17]([CH3:28])=[CH:16][C:15]([CH3:29])=[C:14]([CH:19]=2)[C:13]([NH:60][CH2:61][C:62]2([CH2:66][NH:67][C:68]([C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=3)([C:69]3[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=3)[C:75]3[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=3)[CH2:65][O:64][CH2:63]2)=[O:30])[CH:25]=[C:24]([Cl:26])[N:23]=1
Reactant: NCC1(CNC(c2ccccc2)(c2ccccc2)c2ccccc2)COC1
Reactant: Cc1cc(C)c(-c2cc(Cl)nc(N)n2)cc1C(=O)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C1CCC(=O)N1O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(C)c(-c2cc(Cl)nc(N)n2)cc1C(=O)NCC1(CNC(c2ccccc2)(c2ccccc2)c2ccccc2)COC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 82.8 %

Procedure:
Trifluoroacetic acid (0.67 ml) was added to a dichloromethane (2.0 ml) solution of 5-(2-amino-6-chloropyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (100 mg, 0.33 mmol) obtained in Step 4 of Example 1-1. The mixture was stirred at room temperature for four hours, and then concentrated under reduced pressure. The resulting white solid material was dissolved in N,N-dimethylformamide (1.0 ml), and then diisopropylethylamine (0.105 ml, 0.603 mmol), N-hydroxysuccinimide (38 mg, 0.333 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (64 mg, 0.335 mmol) were added thereto. The mixture was stirred at room temperature for 5.5 hours, and then an N,N-dimethylformamide (2.0 ml) solution of (3-aminomethyloxetan-3-ylmethyl)tritylamine (160 mg, 0.446 mmol) obtained in Step 1 above was added thereto. The prepared reaction solution was stirred at room temperature for 17 hours. A saturated aqueous sodium chloride solution (20 mL) was added to the reaction solution, and extracted three times with ethyl acetate (20 ml). The extract was sequentially washed three times with a saturated aqueous sodium bicarbonate solution (30 ml) and then three times with a saturated aqueous sodium chloride solution (30 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield 5-(2-amino-6-chloropyrimidin-4-yl)-2,4-dimethyl-N-{3-[(tritylamino)methyl]oxetan-3-ylmethyl}benzamide (169 mg) as a white solid material.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:14]2[O:15][C:16]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:17]=3[N:18]=2)[C:7]([NH:10][CH2:11][CH2:12][CH3:13])=[CH:8][CH:9]=1)([O-:3])=[O:2].[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1>>[N+:1]([C:4]1[CH:5]=[C:6]([C:14]2[O:15][C:16]3[CH:22]=[CH:21][C:20]([C:28]4[CH:29]=[CH:30][C:25]([Cl:24])=[CH:26][CH:27]=4)=[CH:19][C:17]=3[N:18]=2)[C:7]([NH:10][CH2:11][CH2:12][CH3:13])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: CCCNc1ccc([N+](=O)[O-])cc1-c1nc2cc(Br)ccc2o1
Product: CCCNc1ccc([N+](=O)[O-])cc1-c1nc2cc(-c3ccc(Cl)cc3)ccc2o1

Procedure:
Prepared by the method of Example 15d), from 2-(3-nitro-6-propylaminophenyl)-5-bromobenzoxazole (400 mg, 1.59 mmol) and 4-chlorophenylboronic acid (258 mg, 1.65 mmol) the subtitle compound was obtained (284 mg, 64%). MS 408.2 m/z (M+H)+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:46])[NH:7][CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]3[N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:20]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=5)[N:24]([CH3:35])[CH:23]=4)=[CH:21][C:14]=23)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[OH-].[K+]>>[C:1]([O:5][C:6](=[O:46])[NH:7][CH:8]1[CH2:9][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][N:16]=[C:15]3[NH:19][C:20]([C:22]4[C:30]5[C:25](=[CH:26][C:27]([O:33][CH3:34])=[C:28]([O:31][CH3:32])[CH:29]=5)[N:24]([CH3:35])[CH:23]=4)=[CH:21][C:14]=23)[CH2:11]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1cc2c(-c3cc4c(CN5CC(NC(=O)OC(C)(C)C)C5)ccnc4n3S(=O)(=O)c3ccc(C)cc3)cn(C)c2cc1OC
Agent: [K+]
Agent: [OH-]
Product: COc1cc2c(-c3cc4c(CN5CC(NC(=O)OC(C)(C)C)C5)ccnc4[nH]3)cn(C)c2cc1OC
Yield: 70.7 %

Procedure:
{1-[2-(5,6-Dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]azetidin-3-yl}carbamic acid tert-butyl ester is prepared as described in Example 179a starting with 0.13 g of {1-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]azetidin-3-yl}carbamic acid tert-butyl ester instead of the [2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl](4-trifluoromethylsulfanylbenzyl)amine used in Example 179a and 0.805 cm3 of 5N potassium hydroxide. 0.07 g of {1-[2-(5,6-dimethoxy-1-methyl-1H-indol-3-yl)-1H-pyrrolo[2,3-b]pyrid-4-ylmethyl]azetidin-3-yl}carbamic acid tert-butyl ester is obtained, the characteristics of which are as follows:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:8])[C:4](=O)[CH2:5]Cl.[N+:9]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:20]=1[NH:19][C:18]([C:21](=[S:23])[NH2:22])=[CH:17]2)([O-:11])=[O:10]>>[CH3:1][O:2][C:3]([C:4]1[N:22]=[C:21]([C:18]2[NH:19][C:20]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[CH:13][C:12]=3[N+:9]([O-:11])=[O:10])[S:23][CH:5]=1)=[O:8]
Reactant: COC(=O)C(=O)CCl
Reactant: NC(=S)c1cc2cccc([N+](=O)[O-])c2[nH]1
Product: COC(=O)c1csc(-c2cc3cccc([N+](=O)[O-])c3[nH]2)n1

Procedure:
3-Chloro-2-oxo-propionic acid methyl ester and 7-nitro-1H-indole-2-carbothioic acid amide prepared in Step A of Preparation 110 were reacted according to the same procedure as Preparation 110 to give the title compound.
Reaction SMILES: [CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([F:16])([F:15])[F:14])=[CH:10][CH:11]=2)[C:6]([NH:17][CH2:18][C:19]([NH:21][CH:22]2[CH2:25][NH:24][CH2:23]2)=[O:20])=[N:5]1)[CH:2]=[CH2:3].[CH:26]1([CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]2)[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1>>[CH2:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([F:16])([F:14])[F:15])=[CH:10][CH:11]=2)[C:6]([NH:17][CH2:18][C:19]([NH:21][CH:22]2[CH2:23][N:24]([CH:36]3[CH2:37][CH2:38][CH:33]([CH:26]4[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]4)[CH2:34][CH2:35]3)[CH2:25]2)=[O:20])=[N:5]1)[CH:2]=[CH2:3]
Reactant: O=C1CCC(C2CCCCC2)CC1
Reactant: C=CCn1nc(NCC(=O)NC2CNC2)c2cc(C(F)(F)F)ccc21
Product: C=CCn1nc(NCC(=O)NC2CN(C3CCC(C4CCCCC4)CC3)C2)c2cc(C(F)(F)F)ccc21

Procedure:
The title compound was prepared as a white solid from reaction of 2-(1-allyl-5-trifluoromethyl-1H-indazol-3-ylamino)-N-azetidin-3-yl-acetamide and bicyclohexyl-4-one using the procedure described in Step E of Example 1.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:8]([OH:10])=O)=[C:5]([CH3:7])[N:6]=1.[NH2:11][C:12]1[CH:13]=[C:14]([CH:31]=[CH:32][C:33]=1[CH3:34])[O:15][C:16]1[CH:17]=[CH:18][C:19]2[N:20]([CH:22]=[C:23]([NH:25][C:26]([CH:28]3[CH2:30][CH2:29]3)=[O:27])[N:24]=2)[N:21]=1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)CC)C>CN(C)C=O>[CH:28]1([C:26]([NH:25][C:23]2[N:24]=[C:19]3[CH:18]=[CH:17][C:16]([O:15][C:14]4[CH:31]=[CH:32][C:33]([CH3:34])=[C:12]([NH:11][C:8]([C:4]5[S:3][C:2]([CH3:1])=[N:6][C:5]=5[CH3:7])=[O:10])[CH:13]=4)=[N:21][N:20]3[CH:22]=2)=[O:27])[CH2:29][CH2:30]1
Reactant: Cc1ccc(Oc2ccc3nc(NC(=O)C4CC4)cn3n2)cc1N
Reactant: Cc1nc(C)c(C(=O)O)s1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1nc(C)c(C(=O)Nc2cc(Oc3ccc4nc(NC(=O)C5CC5)cn4n3)ccc2C)s1
Yield: 41.8 %

Procedure:
In the same manner as in Example 261 and using 2,4-dimethyl-1,3-thiazole-5-carboxylic acid (130 mg, 0.80 mmol), N-[6-(3-amino-4-methylphenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (200 mg, 0.62 mmol), 1-hydroxybenzotriazole (110 mg, 0.80 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (150 mg, 0.80 mmol), triethylamine (94 mg, 0.93 mmol) and N,N-dimethylformamide (5 mL) as starting materials, the title compound (120 mg, 41%) was obtained as a pale-yellow solid.
Reaction SMILES: [ClH:1].[CH2:2]1[CH:11]2[CH:6]([CH2:7][CH2:8][CH2:9][CH2:10]2)[CH2:5][CH2:4][CH:3]1[N:12]1[CH2:28][CH2:27][C:15]2([N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:18][NH:17][C:16]2=[O:26])[CH2:14][CH2:13]1.[H-].[Na+].[CH3:31]I>CN(C=O)C>[ClH:1].[CH2:2]1[CH:11]2[CH:6]([CH2:7][CH2:8][CH2:9][CH2:10]2)[CH2:5][CH2:4][CH:3]1[N:12]1[CH2:28][CH2:27][C:15]2([N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:18][N:17]([CH3:31])[C:16]2=[O:26])[CH2:14][CH2:13]1
Reactant: O=C1NCN(c2ccccc2)C12CCN(C1CCC3CCCCC3C1)CC2
Reactant: CI
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CN(c2ccccc2)C2(CCN(C3CCC4CCCCC4C3)CC2)C1=O
Temperature: 80 °C
Reaction time: 1 h

Procedure:
8-(Decahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one hydrochloride (1:1) (1.2 mmol) was suspended in DMF (20 ml). Sodium hydride (2.4 mmol) was added and the mixture was stirred at 80° C. for 1 h. The mixture was cooled to room temperature, methyl iodide (1.2 mmol) was added and the mixture was stirred for 18 h. DMF was evaporated, sodium bicarbonate and ethylacetate were added. The organic phase was washed with brine, dried with MgSO4 and concentrated. Chromatography on silica gel (methylenchloride/methanol, 98:2) yielded the desired product which was crystallized as its HCl-salt from ethylacetate/ethanol. 0.19 g (36%) 8-(decahydro-naphthalen-2-yl)-3-methyl-1-phenyl-1,3,8-triaza-spiro[4,5]decan-4-one hydrochloride (1:1) as a colorless solid, m.p.>250° C. and MS: m/e=382 (M+H+).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl-].[NH4+:17]>CO>[NH2:17][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: FC(F)(F)c1ccc2c(Cl)ccnc2c1
Agent: [Cl-]
Solvent: CO
Product: Nc1ccnc2cc(C(F)(F)F)ccc12

Procedure:
A solution of 4-chloro-7-trifluoromethylquinoline (1 g) and ammonium chloride (1 g) in methanol (10 mL) was heated at 70° C. overnight. Then the solid was filtered off and washed with methanol. The filtrated was evaporated to give 4-amino-7-trifluoromethylquinoline. LCMS: ret. time: 14.81 min.; purity: 82.25%; MS (m/e): 228.11 (M+16).