Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].C(OC([N:28]1[CH2:33][CH2:32][CH:31]([N:34]([C:36]([C:38]2[CH:39]=[N:40][C:41]([NH2:44])=[CH:42][CH:43]=2)=[O:37])[CH3:35])[CH2:30][CH2:29]1)=O)(C)(C)C>>[CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10]([NH:44][C:41]3[CH:42]=[CH:43][C:38]([C:36](=[O:37])[N:34]([CH3:35])[CH:31]4[CH2:32][CH2:33][NH:28][CH2:29][CH2:30]4)=[CH:39][N:40]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CN(C(=O)c1ccc(N)nc1)C1CCN(C(=O)OC(C)(C)C)CC1
Reactant: CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(C(=O)N(C)C4CCNCC4)cn3)nc2n1C1CCCC1
Yield: 16.2 %

Procedure:
Following Buchwald Method B, 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (170 mg, 0.58 mmol) and 4-[(6-amino-pyridine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (292 mg, 0.87 mmol), followed by deprotection using General Procedure A to give 7-cyclopentyl-2-[5-(methyl-piperidin-4-yl-carbamoyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (46 mg, 16%). MS (ESI) m/z 491.3 (M+H)+
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[C:5]([NH:7][C:8]1[C:9](Cl)=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=1)=[O:6].[CH2:19]([O:21][C:22](=[O:30])[CH2:23][N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)[CH3:20]>>[CH2:19]([O:21][C:22](=[O:30])[CH2:23][N:24]1[CH2:29][CH2:28][N:27]([C:9]2[C:8]([NH:7][C:5](=[O:6])[C:4]3[CH:16]=[CH:17][CH:18]=[C:2]([Cl:1])[CH:3]=3)=[CH:13][C:12]([Cl:14])=[CH:11][N:10]=2)[CH2:26][CH2:25]1)[CH3:20]
Reactant: O=C(Nc1cc(Cl)cnc1Cl)c1cccc(Cl)c1
Reactant: CCOC(=O)CN1CCNCC1
Product: CCOC(=O)CN1CCN(c2ncc(Cl)cc2NC(=O)c2cccc(Cl)c2)CC1
Temperature: 105 °C
Reaction time: 20 h
Yield: 82.4 %

Procedure:
A mixture of 5.00 g (16.6 mmol) of 3-chloro-N-(2,5-dichloro-pyridin-3-yl)-benzamide and 4.26 g (24.9 mmol) of piperazin-1-yl-acetic acid ethyl ester in a solvent free condition is heated to 105° C. and stirred for 20 hours. The residue is purified by flash silica gel chromatography to give 5.98 g (82.6%) of {4-[5-chloro-3-(3-chloro-benzoylamino)-pyridin-2-yl]-piperazin-1-yl}-acetic acid ethyl ester as a light yellow solid.
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[C:14]([C:28]4[CH:33]=[CH:32][C:31]([O:34]C)=[CH:30][CH:29]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]5[CH2:27][CH2:26][CH2:25][CH2:24]5)[N:17]=4)=[C:9]3[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.B(Br)(Br)Br>ClCCl>[CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[C:14]([C:28]4[CH:29]=[CH:30][C:31]([OH:34])=[CH:32][CH:33]=4)[C:15]([C:16]4[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]5[CH2:24][CH2:25][CH2:26][CH2:27]5)[N:17]=4)=[C:9]3[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(-c2nn3ccc(NC4CCCC4)cc3c2-c2ccnc(NC3CCCC3)n2)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: Oc1ccc(-c2nn3ccc(NC4CCCC4)cc3c2-c2ccnc(NC3CCCC3)n2)cc1
Yield: 80.2 %

Procedure:
Treatment of N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-5-amine (500 mg, 1.07 mmol) in dichloromethane with boron tribromide, followed by aqueous workup, gave 4-{5-(cyclopentylamino)-3-[2-(cyclopentylamino)-4-pyrimidinyl]pyrazolo[1,5-α]pyridin-2-yl}phenol (390 mg, 81%) as a yellow solid. 1H NMR (CD3OD) δ 8.16 (d, 1H), 7.85 (d, 1H), 7.40 (m, 3H), 6.90 (d, 2H), 6.53 (dd, 1H), 6.27 (d, 1H), 4.44 (m, 1H), 3.92 (m, 1H), 2.11 (m, 4H), 1.84–1.58 (m, 12H). MS m/z 455 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:29].Cl>O1CCOCC1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:30])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][NH:14][CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:29]
Reactant: COC(=O)/C=C/c1cc(F)c2c(c1)C(=O)CC1(CCN(C(=O)OC(C)(C)C)CC1)O2
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: COC(=O)/C=C/c1cc(F)c2c(c1)C(=O)CC1(CCNCC1)O2
Temperature: 25 °C
Reaction time: 5 h

Procedure:
A mixture of (E)-3-{1′-tert-butoxycarbonyl-8-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (2.78 g, 6.63 mmol) and 4 M HCl in dioxane (3 ml) in DCM (50 ml) was stirred at RT for 5 h. The solvent was removed, the residue was triturated in DCM and filtered to give the title compound as its hydrochloride salt (2.04 g).
Reaction SMILES: [CH3:1][C:2](=[O:7])[CH2:3][C:4](=[O:6])[CH3:5].Br[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CS(C)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>[C:4]([CH:3]([C:2](=[O:7])[CH3:1])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:6])[CH3:5]
Reactant: CC(=O)CC(C)=O
Reactant: CCOC(=O)CCCCCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [K+]
Solvent: CC#N
Solvent: CS(C)=O
Product: CCOC(=O)CCCCCCC(C(C)=O)C(C)=O
Temperature: 20 °C
Reaction time: 8 h
Yield: 458.4 %

Procedure:
A mixture of pentane-2,4-dione (5.0 g), ethyl 7-bromoheptanoate (11.1 g), potassium carbonate (13.8 g), and cesium carbonate (1.63 g) in a mixture of acetonitrile (150 ml) and dimethylsulfoxide (30 ml) was stirred at 20° C. overnight, then pentane-2,4-dione (5 g) was added. After stirring at 20° C. overnight, the mixture was partitioned between ethyl acetate and 0.5N hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give ethyl 8-acetyl-9-oxodecanoate (55 g) as an oil.
Reaction SMILES: [C:1]([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH3:24])[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[C:1]([O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([C:18]2[CH:19]=[CH:20][C:15]([CH3:24])=[CH:16][CH:17]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccc(B(O)O)cc1
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cc1
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: Cc1ccccc1
Solvent: O
Product: Cc1ccc(-c2ccc(C(=O)OC(C)(C)C)cc2)cc1
Yield: 79.5 %

Procedure:
To a mixture of tert-butyl-4-bromobenzoate (40 g, 0.15 mol), 4-tolylboronic acid (23.3 g, 0.17 mol) and sodium carbonate (150 g) in toluene (350 mL) and water (350 mL) was added tetrakis(triphenylphosphine)palladium(0) (8.7 g, 0.007 mol) and the reaction mixture was refluxed for 10 h under nitrogen atmosphere. The organic layer was separated, washed with water, dried and concentrated to give tert-butyl-4-(4-tolyl)benzoate (32 g, 77%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C:9]1[N:10]=[CH:11][C:12]([N:36]2[CH2:41][C@H:40]3[C@H:38]([CH:39]3[C:42]([O:44]CC)=[O:43])[CH2:37]2)=[N:13][C:14]=1[C:15]1[O:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:28])=[CH:22][CH:21]=2)=[N:18][N:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[OH-].[Na+]>CO>[C:1]([O:5][C:6]([N:8]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[C:9]1[N:10]=[CH:11][C:12]([N:36]2[CH2:41][C@H:40]3[C@H:38]([CH:39]3[C:42]([OH:44])=[O:43])[CH2:37]2)=[N:13][C:14]=1[C:15]1[O:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH3:28])=[CH:22][CH:21]=2)=[N:18][N:19]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(=O)C1[C@H]2CN(c3cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(-c4nnc(-c5ccc(CN(C)C(=O)OC(C)(C)C)cc5)o4)n3)C[C@@H]12
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CN(Cc1ccc(-c2nnc(-c3nc(N4C[C@@H]5C(C(=O)O)[C@@H]5C4)cnc3N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)o2)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of ethyl (1R,5S)-3-[5-[bis(tert-butoxycarbonyl)amino]-6-[5-[4-[[tert-butoxycarbonyl(methyl)amino]methyl]phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxylate (270 mg, 0.37 mmol) in of 2:1 THF: MeOH (1 mL) was added NaOH (550 μL, of 1 M, 0.55 mmol). The reaction mixture was stirred for 30 minutes at room temperature. The solvent was evaporated to obtain (1R,5S)-3-[5-[bis(tert-butoxycarbonyl)amino]-6-[5-[4-[[tert-butoxycarbonyl(methyl)amino]methyl]phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-3-azabicyclo[3.1.0]hexane-6-carboxylic acid, which was used for the next step without further purification.
Reaction SMILES: [F:1][CH2:2][CH:3]([N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][OH:13])[CH2:8][CH2:7]1)[CH2:4][F:5].[H-].[Na+].F[C:17]1[CH:22]=[CH:21][C:20]([S:23]([NH2:26])(=[O:25])=[O:24])=[CH:19][C:18]=1[N+:27]([O-:29])=[O:28].O>O1CCCC1>[F:5][CH2:4][CH:3]([N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][O:13][C:17]2[CH:22]=[CH:21][C:20]([S:23]([NH2:26])(=[O:25])=[O:24])=[CH:19][C:18]=2[N+:27]([O-:29])=[O:28])[CH2:8][CH2:7]1)[CH2:2][F:1]
Reactant: OCC1CCN(C(CF)CF)CC1
Reactant: NS(=O)(=O)c1ccc(F)c([N+](=O)[O-])c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: NS(=O)(=O)c1ccc(OCC2CCN(C(CF)CF)CC2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of (1-(1,3-difluoropropan-2-yl)piperidin-4-yl)methanol (0.068 g) in tetrahydrofuran (1 mL) was added sodium hydride (0.056 g) and the reaction stirred for 30 minutes at room temperature. 4-Fluoro-3-nitrobenzenesulfonamide (0.077 g) was added in one portion and stirring was continued for 1 hour. The reaction was poured into water (20 mL) and extracted with dichloromethane. The pH of the aqueous layer was adjusted to pH˜8 and it was extracted with dichloromethane (50 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated to give the title compound.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:28])[C:9]([C:15]2[CH:16]=[C:17]([F:27])[C:18]3[O:23][CH2:22][C:21](=[O:24])[N:20]([CH3:25])[C:19]=3[CH:26]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:29])[CH:3]=1.[F:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][C:36]=1[C:37]([O:39][CH3:40])=[O:38]>>[CH3:40][O:39][C:37]([C:36]1[CH:35]=[CH:34][C:33]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:28])[C:9]([C:15]3[CH:16]=[C:17]([F:27])[C:18]4[O:23][CH2:22][C:21](=[O:24])[N:20]([CH3:25])[C:19]=4[CH:26]=3)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:29])[CH:3]=2)=[CH:32][C:31]=1[F:30])=[O:38]
Reactant: CC(c1ccc(Br)cc1Cl)C(O)(c1cc(F)c2c(c1)N(C)C(=O)CO2)C(F)(F)F
Reactant: COC(=O)c1ccc(B(O)O)cc1F
Product: COC(=O)c1ccc(-c2ccc(C(C)C(O)(c3cc(F)c4c(c3)N(C)C(=O)CO4)C(F)(F)F)c(Cl)c2)cc1F

Procedure:
In analogy to Example 17, step 2, 6-[2-(4-bromo-2-chloro-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-8-fluoro-4-methyl-4H-benzo[1,4]oxazin-3-one was reacted with 3-fluoro-4-methoxycarbonylphenylboronic acid to give the title compound as a colorless foam. MS (m/e)=570.3 [M+H+].
Reaction SMILES: [F:1][C:2]1[CH:17]=[C:16]([CH:18]=O)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1.[S:20]1[CH:24]=[CH:23][CH:22]=[C:21]1[CH2:25][CH2:26][NH2:27].[BH4-].[Na+]>CO>[F:1][C:2]1[CH:17]=[C:16]([CH2:18][NH:27][CH2:26][CH2:25][C:21]2[S:20][CH:24]=[CH:23][CH:22]=2)[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]([C:11]([NH2:13])=[O:12])=[N:9][CH:10]=1
Reactant: NCCc1cccs1
Reactant: NC(=O)c1cnc(Oc2ccc(C=O)cc2F)cn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: NC(=O)c1cnc(Oc2ccc(CNCCc3cccs3)cc2F)cn1
Reaction time: 8 h
Yield: 17.6 %

Procedure:
Place 5-(2-fluoro-4-formylphenoxy)pyrazine-2-carboxamide (Example 737, Part E) (0.400 g, 1.53 mmol), 2-(2-thienyl)ethylamine (0.217 g, 1.68 mmol) and 3 Å molecular sieves in a vial. Add methanol (7.7 mL), cap and stir overnight. Add NaBH4 (0.058 g, 1.53 mmol) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 15% (2.0 M NH3 in methanol) in 80% (ethyl acetate in hexanes). Concentrate the fractions containing the product. Take the solid up in dichloromethane (100 mL) and wash with 1.0 N NaOH (2×25 mL) to give the title compound (0.100 g, 18%): TOF MS ES+ 373.1 (M+H)+, HRMS calcd for C15H11N4O2FS 373.1135 (M+H)+, found 373.1150, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min. 20-95% over 18], tR=10.3 min. 100% purity.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=O.[CH3:17][NH2:18].[BH4-].[Na+].O>CO>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([CH:9]([NH:18][CH3:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:4]=1
Reactant: CN
Reactant: Nc1ccc(Br)cc1C(=O)c1ccccn1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CNC(c1ccccn1)c1cc(Br)ccc1N
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of (2-Amino-5-bromo-phenyl)-pyridin-2-yl-methanone (500 mg, 1.8 mmol) in MeOH (20 mL) is added Ti(i-OPr)4 (1.0 g, 3.6 mmol) and methylamine (2M in THF, 4.5 mL). Then the mixture is stirred at room temperature for 6 h. Sodium borohydride (137 mg, 3.6 mmol) is added in one portion. The mixture is stirred at room temperature for 2 h. Water (10 mL) is added and the mixture is filtered and washed with EtOAc. The filtrate is washed with brine, the organic layer is concentrated in vacuum to give the desired product as a crude mixture. This is used in next step with no further purification.
Reaction SMILES: [CH3:1][Si:2]([O:7][CH3:8])([O:5][CH3:6])[O:3][CH3:4].[CH2:9]([Si:12]([CH3:19])([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])CC.[CH2:20]([Si](C)(Cl)Cl)[CH2:21][CH3:22].[OH-:27].[K+:28]>O.C(O)C.CO>[CH3:1][Si:2]([O:7][CH3:8])([O:5][CH3:6])[O:3][CH3:4].[CH2:20]([CH:17]([O:16][Si:12]([CH3:9])([CH3:19])[O:13][CH2:14][CH3:15])[CH3:18])[CH2:21][CH3:22].[OH-:27].[K+:28]
Reactant: CCC[Si](C)(OCC)OCC
Reactant: CCC[Si](C)(Cl)Cl
Agent: CO[Si](C)(OC)OC
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: CO
Product: CCCC(C)O[Si](C)(C)OCC

Procedure:
A 500 ml 5-neck round-bottom flask, inertized with nitrogen and fitted with paddle stirrer, dropping funnel, thermometer, and water separator with reflux condenser, is charged with 27 g (0.198 mol) of methyltrimethoxysilane (available commercially from Wacker Chemie AG), 3.9 g (0.02) of n-propyl(methyl)diethoxysilane (prepared in the laboratory by reacting n-propyl(methyl)dichlorosilane with ethanol) and 20 g of Isopar E (isoparaffinic hydrocarbon mixture with a boiling range of 113-143° C., available commercially from ExxonMobil). The water separator is filled to the brim with Isopar E. Accompanied by stirring at 350 rpm, a solution of 12.4 g (0.188 mol) of potassium hydroxide (85% form, available commercially from AppliChem) in 7.9 g (0.44 mol) of demineralized water is metered in over 12 minutes. The mixture heats up to 48° C. It is heated to boiling temperature. The distillate separates off as the bottom phase in the water separator. Up to a boiling temperature of 95° C., 19.4 g of colorless, slightly turbid distillate accumulate, containing—according to analysis by gas chromatography—78.5% of methanol, 7.5% of ethanol, 3.5% of water, and 8.2% of Isopar E. The bottom phase is drained off from the water separator, which is made up completely with Isopar E again, and water is removed in circulation at a boiling temperature of up to 131° C. This produces 6.2 g of distillate as bottom phase, which according to GC analysis contains 46.9% of methanol, 4.7% of ethanol, and 48.4% of water. During the distillation, a pastelike white solid separates out in the reaction mixture, and breaks down increasingly into fine particles and forms a suspension. 10 g of cyclohexane are added and the suspension is filtered through a Beco KD3 filter plate in a pressure suction filter, and nitrogen is passed through to constant weight. This gives 21.4 g of fine, white, free-flowable powder with a solids content of 99.5% (determined using the HR73 halogen moisture analyzer from Mettler Toledo at 160° C.). A 50% strength aqueous solution prepared with this solid exhibits no precipitation even after storage at room temperature for two weeks in the absence of air.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[NH:8][C:7](=[O:15])[N:6]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:5]2=[O:21].[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>>[N+:12]([C:11]1[CH:10]=[C:9]2[C:4]([C:5](=[O:21])[N:6]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:7](=[O:15])[NH:8]2)=[CH:3][C:2]=1[N:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1)([O-:14])=[O:13]
Reactant: C1CCNC1
Reactant: CS(=O)(=O)Nn1c(=O)[nH]c2cc([N+](=O)[O-])c(F)cc2c1=O
Product: CS(=O)(=O)Nn1c(=O)[nH]c2cc([N+](=O)[O-])c(N3CCCC3)cc2c1=O
Yield: 35 %

Procedure:
N-(6-Fluoro-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide (30 mg, 0.0943 mmol) is reacted with pyrrolidine according to the GPA affording 12.2 mg (35%) of an orange-light powder. Rt=4.37 min.
Reaction SMILES: C1C2C3=CC4C=CC(C(N)=O)=CC=4N3CC=CC=2C=CC=1.[N:22]1([C:28]([O:30]C(C)(C)C)=O)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.[OH:35][C:36](C)([CH3:40])[C:37](O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.O.C(N(CC)CC)C>[OH:35][C:36]([CH3:40])([CH3:37])[C:28]([N:22]1[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]1)=[O:30]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: CC(C)(O)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(O)C(=O)N1CCNCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 319.3 %

Procedure:
7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(2-hydroxy-2-methyl-l-oxopropyl)-1-piperazinyl]carbonyl]-3-methoxy-. To a solution of tert-butyl piperazine-1-carboxylate (372 mg, 2.0 mmol), 2-hydroxy-2-methylpropanoic acid (229 mg, 2.2 mmol) and triethylamine (1.1 mL) in DMF (7 mL) was added HATU (988 mg, 2.6 mmol). The reaction mixture was stirred at rt for 2 h, then diluted with H2O, neutralized with 1N aqueous HCl (8 mL), concentrated, and the residue was partitioned between EtOAc and H2O. The organic phase was separated, washed with brine and concentrated to a white solid (1.1 g). The solid was dissolved into ClCH2CH2Cl (10 mL) and treated with trifluoroacetic acid (5 mL). The reaction mixture was stirred at rt for 2 h, and concentrated to yield crude 2-hydroxy-2-methyl-1-(piperazin-1-yl)propan-1-one (1.1 g) as yellow semi-solid.
Reaction SMILES: [OH-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([NH:11][N:12]=[C:13]2[C:17](=[O:18])[O:16][C:15]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:14]2)[CH:8]=[CH:9][CH:10]=1.CC(C)=O.Cl>C(C(C)=O)C.CN(C)C=O.O1CCCC1.O1CCOCC1>[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([N:11]2[C:15]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:14][C:13]([C:17]([OH:16])=[O:18])=[N:12]2)[CH:8]=[CH:9][CH:10]=1
Reactant: O=C1OC(c2ccccc2)=NC1=NNc1cccc(CO)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CC(C)=O
Solvent: C1COCCO1
Product: O=C(O)c1nc(-c2ccccc2)n(-c2cccc(CO)c2)n1
Temperature: 100 °C

Procedure:
Sodium hydroxide in an amount of more than equivalent is added to the above-mentioned 4-[3-(hydroxymethyl)phenylhydrazono]-2-phenyl-2-oxazolin-5-one in an aprotic organic solvent such as acetone, dioxane, tetrahydrofuran, dimethylformamide and methyl ethyl ketone and after reacting the mixture, hydrochloric acid is added to the mixture to adjust the pH to from 1 to 4, and then the thus adjusted mixture is heated to a temperature of lower than 100° C., preferably from 30° to 60° C., thereby obtaining a novel compound, 1-[3-(hydroxymethyl)phenyl]-5-phenyl-1H-1,2,4,-triazole-3-carboxylic acid represented by the formula (V): ##STR87##
Reaction SMILES: [C:1]([O:4][CH:5]1[CH2:9][CH2:8][CH:7]=[CH:6]1)(=O)[CH3:2].[CH:10]1(O)[CH2:15]CC[CH:12]=[CH:11]1.O>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CC(C)=O>[CH:5]1([O:4][CH:1]2[CH2:12][CH2:11][CH2:10][CH:15]=[CH:2]2)[CH2:9][CH2:8][CH:7]=[CH:6]1
Reactant: OC1C=CCCC1
Reactant: CC(=O)OC1C=CCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Solvent: CC(C)=O
Solvent: O
Product: C1=CC(OC2C=CCC2)CCC1
Temperature: 40 °C
Reaction time: 4 h

Procedure:
A two-phase reaction mixture containing 2-cyclopentenyl acetate (0.30 g, 2.4 millimols), 2-cyclohexenol (0.50 g, 5.1 millimols), tetrabutylammonium hydrogen sulfate (0.020 g, 0.06 millimols), and water (0.25 g, 13.9 millimols) was heated at 40° C with vigorous stirring for four hours. Acetone was then added to give a one-phase system for analytical purposes, and the solution was analyzed by gas chromatography using an Apiezon column programmed from 60 to 220° C. The following relative peak areas were observed for the cyclic components:
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:23]=[CH:22][C:16]([O:17][CH2:18][CH2:19][C:20]#[N:21])=[CH:15][CH:14]=1.[N-:24]=[N+:25]=[N-:26].[Na+].[Cl-].[NH4+].[OH-].[Na+]>CN(C)C=O>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][C:13]1[CH:23]=[CH:22][C:16]([O:17][CH2:18][CH2:19][C:20]2[NH:26][N:25]=[N:24][N:21]=2)=[CH:15][CH:14]=1
Reactant: N#CCCOc1ccc(OCc2ccc3ccccc3n2)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc2nc(COc3ccc(OCCc4nnn[nH]4)cc3)ccc2c1

Procedure:
A mixture of 9.8 g (0.032 mol) of 3-[4-(2-quinolylmethyloxy)phenoxy]propionitrile, 6.36 g of sodium azide and 5.28 g of ammonium chloride is heated with 30 ml of dry dimethylformamide at 140° C. for 20 hours. The reaction mixture is poured onto ice, basified with 1N sodium hydroxide and extracted 2 times with ethyl acetate. The aqueous fraction is acidified with acetic acid. The product is filtered and washed with water. The crude product is crystallized from acetonitrile to give 5-[2-(4-(2-quinolylmethyloxy)phenoxy)ethyl]tetrazole.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[C:14]3[C:19]=1[CH:18]=[CH:17][CH:16]=[N:15]3)[NH:12][S:11](=[O:21])(=[O:20])[C:10]1[C:5]2=[CH:6][C:7]([C:22](O)=[O:23])=[CH:8][CH:9]=1.[NH2:25][CH:26]([CH2:29][OH:30])[CH2:27][OH:28].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[OH:28][CH2:27][CH:26]([NH:25][C:22]([C:7]1[CH:6]=[C:5]2[C:10]([S:11](=[O:20])(=[O:21])[NH:12][C:13]3[C:4]2=[CH:3][C:2]([Cl:1])=[C:19]2[C:14]=3[N:15]=[CH:16][CH:17]=[CH:18]2)=[CH:9][CH:8]=1)=[O:23])[CH2:29][OH:30]
Reactant: O=C(O)c1ccc2c(c1)-c1cc(Cl)c3cccnc3c1NS2(=O)=O
Reactant: NC(CO)CO
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(NC(CO)CO)c1ccc2c(c1)-c1cc(Cl)c3cccnc3c1NS2(=O)=O
Yield: 34.1 %

Procedure:
In a similar fashion using route 54 general procedure 123, 12-chloro-6,6-dioxo-5,6-dihydro-6λ*6*-thia-4,5-diaza-chrysene-9-carboxylic acid 524 (100 mg, 0.27 mmol), serinol (50 mg, 0.55 mmol), EDC.HCl (80 mg, 0.41 mmol), HOBt (56 mg, 0.41 mmol), TEA (0.12 ml, 0.11 mmol) and DMF (1 ml) gave the title compound (40 mg, 33%) after purification by column chromatography with chloroform/MeOH (90:10) as the eluent.