Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7](Br)[CH:6]=1)[CH3:2].[F:13][C:14]([F:26])([F:25])[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[O:15][C:14]([F:13])([F:26])[F:25])[CH:6]=1)[CH3:2]
Reactant: OB(O)c1ccccc1OC(F)(F)F
Reactant: CCOC(=O)c1cccc(Br)c1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1cccc(-c2ccccc2OC(F)(F)F)c1

Procedure:
To a solution of 0.94 g (4.58 mmol) of ethyl-3-bromobenzoate in 14.5 mL of toluene at RT was added 0.25 g (0.218 mmol) of tetrakis(triphenylphosphine) palladium(0), 0.94 g (4.58 mmol) of 2-trifluoromethoxyphenylboronic acid, 2.22 mL (4.45 mmol) of 2M aqueous sodium carbonate solution and 7 mL of ethanol. The reaction mixture was heated at reflux for 18 h. The reaction mixture was cooled and diluted with ethyl acetate and water. The organic fraction was separated and washed with saturated NaCl solution (brine), dried over MgSO4, and filtered. The filtrate was concentrated to an oil which was purified by chromatography (silica, 1%, 5%, 30% successively ethyl acetate: hexanes) to give the title compound. 1H NMR (CD3OD) (δ, ppm): 8.02 (s, 1H), 7.97 (dd, J=7.8, 1.2 Hz, 1H), 7.60 (dd, J=7.7, 1.3 Hz, 1H), 7.50-7.33 (m, 5H), 4.31(q, 2H), 1.31(t, 3H). Mass Spectrum (ESI) m/e (M+1): 311.2.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([NH2:7])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:3]=1.I[C:15]1[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(O)(=O)C>[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:15]2[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=2[C:17]([OH:19])=[O:18])[N:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[N:3]=1
Reactant: O=C(O)c1ccccc1I
Reactant: Cc1cc(N)n(-c2ccccn2)n1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(Nc2ccccc2C(=O)O)n(-c2ccccn2)n1
Temperature: 25 °C
Yield: 97.9 %

Procedure:
A solution of 3-methyl-1-(2-pyridinyl)-1H-pyrazol-5-ylamine (5.23 g, 30 mmol), o-iodobenzoic acid (8.93 g, 36 mmol), copper acetate (II) (0.654 g, 3.6 mmol), and potassium carbonate (4.98 g, 36 mmol) in N,N-dimethylformamide (30 mL) was heated under reflux for 1 hour under an argon atmosphere. After the solution was cooled to room temperature, the mixture was added to water. The solution was made weakly acidic by the addition of acetic acid, and the resulting crude crystals were collected by filtration. The crystals were washed with water and air dried to give the title compound (8.64 g, 98% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]([CH3:20])([CH3:19])[C:15]([O:17][CH3:18])=[O:16])=[N:11][C:10]=1[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[C:23]([OH:30])[N:22]=1>CO.[Pd]>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:10]2[N:11]=[C:12]([C:14]([CH3:20])([CH3:19])[C:15]([O:17][CH3:18])=[O:16])[NH:13][C:9]=2[C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[N:22][C:23]=1[OH:30]
Reactant: COC(=O)C(C)(C)c1nc(-c2ccc([N+](=O)[O-])c(O)n2)c(-c2ccc(F)cc2F)[nH]1
Agent: [Pd]
Solvent: CO
Product: COC(=O)C(C)(C)c1nc(-c2ccc(N)c(O)n2)c(-c2ccc(F)cc2F)[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.9 %

Procedure:
A mixture of methyl 2-[5-(2,4-difluorophenyl)-4-(6-hydroxy-5-nitro-2-pyridyl)-1H-imidazol-2-yl]-2-methyl-propanoate (49.5 g, 118.32 mmol) and palladium 5% weight (dry basis) on activated carbon (4.95 g, 2.33 mmol) in methanol (1.18 L) is stirred under a hydrogen atmosphere (balloon) at RT overnight. The suspension is filtered through CELITE®, rinsed with methanol, and the filtrate is concentrated under reduced pressure to afford the crude title compound (39 g) as a brown solid.
Reaction SMILES: [CH:1]([CH:9]1[CH2:14][C:13](=[O:15])[O:12][C:10]1=[O:11])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[OH-:16].[K+]>>[CH:1]([CH:9]([CH2:14][C:13]([OH:12])=[O:15])[C:10]([OH:16])=[O:11])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCC=CC1CC(=O)OC1=O
Reactant: [OH-]
Agent: [K+]
Product: CCCCCCC=CC(CC(=O)O)C(=O)O

Procedure:
Octenyl succinic anhydride was added to an aqueous, 45% potassium hydroxide solution, and heated to form the di-potassium salt of 2- octenyl-1,4-butanedioic acid (the friction modifier). A lubricant, methyl 9 EO tallowate, and the friction modifier were mixed together to form a composition having a ratio of 19:1 by weight, respectively.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[N+:11]([O-:13])=[O:12])[C:5]([OH:7])=[O:6].[NH2:14][C:15]1[S:16][C:17]([C:27]([NH2:29])=[O:28])=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>O.CN(C)C=O>[C:27]([C:17]1[S:16][C:15]([NH:14][C:2]2[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=2[N+:11]([O-:13])=[O:12])[C:5]([OH:7])=[O:6])=[N:19][C:18]=1[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=1)(=[O:28])[NH2:29]
Reactant: NC(=O)c1sc(N)nc1-c1cccc(Cl)c1
Reactant: O=C(O)c1ccc([N+](=O)[O-])c(F)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: NC(=O)c1sc(Nc2cc(C(=O)O)ccc2[N+](=O)[O-])nc1-c1cccc(Cl)c1
Reaction time: 16 h
Yield: 55.9 %

Procedure:
A mixture of 0.222 g (1.2 mmole) of 3-fluoro-4-nitrobenzoic acid, 0.30 g (1.2 mmole) of 2-amino-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (V.2), 1.5 g (4.6 mmole) of cesium carbonate and 40 mL of dimethylformamide was stirred at 60 degrees for 16 hours. The mixture was cooled and poured into water. The dark mixture was made acidic by addition of hydrochloric acid, and the resulting orange precipitate was collected by filtration, washing, water to give 0.281 g of 3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazol-2-ylamino]-4-nitro-benzoic acid (VI.10).
Reaction SMILES: COC(=O)C1C=CC=C(C2C=NC(N)=C(C3SC4C=CC=CC=4N=3)C=2)C=1.C[O:28][C:29]([C:31]1[CH:36]=[C:35]([C:37]2[CH:38]=[N:39][C:40]([NH2:52])=[C:41]([C:43]3[S:44][C:45]4[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=4[N:47]=3)[CH:42]=2)[CH:34]=[CH:33][N:32]=1)=[O:30].[OH-].[Na+]>CO>[NH2:52][C:40]1[N:39]=[CH:38][C:37]([C:35]2[CH:34]=[CH:33][N:32]=[C:31]([C:29]([OH:30])=[O:28])[CH:36]=2)=[CH:42][C:41]=1[C:43]1[S:44][C:45]2[CH:51]=[CH:50][CH:49]=[CH:48][C:46]=2[N:47]=1
Reactant: COC(=O)c1cc(-c2cnc(N)c(-c3nc4ccccc4s3)c2)ccn1
Agent: COC(=O)c1cccc(-c2cnc(N)c(-c3nc4ccccc4s3)c2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Nc1ncc(-c2ccnc(C(=O)O)c2)cc1-c1nc2ccccc2s1

Procedure:
Following the procedure for 3-(6-amino-5-benzothiazol-2-ylpyridin-3-yl)-benzoic acid methyl ester, the title compound was prepared from 6-amino-5-benzothiazol-2-yl-[3,4′]bipyridinyl-2′-carboxylic acid methyl ester (1.14 g, 3.2 mmol) and NaOH (0.48 g, 12 mmol) in MeOH (10 mL). 1H NMR (400 MHz, DMSO-d6): δ=13.0 (very brs, 1H), 8.62 (d, J=2.2 Hz, 1H), 8.29 (d, J=2.2 Hz, 1H), 8.19-8.13 (m, 3H), 8.12 (d, J=7.8 Hz, 1H), 8.04-8.00 & 7.88-7.84 (AA′BB′, 4H), 7.57 (ddd, J=1.0, 7.0, 8.0 Hz, 1H), 7.49 (ddd, J=1.0, 7.4, 8.0 Hz, 1H). MS(ES+): m/z=348.08 (100) [MH+]. HPLC: tR=3.29 min (polar—5 min, ZQ2).
Reaction SMILES: [CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[CH2:11]([O:18][NH:19][CH2:20][C:21]1([C:26]([OH:28])=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>ClCCl>[CH2:11]([O:18][N:19]([CH2:20][C:21]1([C:26]([OH:28])=[O:27])[CH2:25][CH2:24][CH2:23][CH2:22]1)[CH:1]=[O:2])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=CO
Reactant: O=C(O)C1(CNOCc2ccccc2)CCCC1
Solvent: CC(=O)OC(C)=O
Solvent: ClCCl
Product: O=CN(CC1(C(=O)O)CCCC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a cold solution of formic acid (10.3 mL, 0.27 mol) in dichloromethane (40 mL) at 0° C. under a nitrogen atmosphere was added acetic anhydride (4.2 mL, 44.1 mmol). After 1 h, a solution of 1-(benzyloxyamino-methyl)-cyclopentanecarboxylic acid (1.1 g, 4.41 mmol) in dichloromethane (20 mL) was added. The mixture was stirred at room temperature for 18 h and was concentrated in vacuo. Water (100 mL) was added and the mixture was extracted with dichloromethane (100 mL×2). The combined organic extracts were dried (MgSO4) and were evaporated in vacuo to yield the title compound as a pale, yellow oil (1.05 g, 86%). MH+278.
Reaction SMILES: C1(C)C(C)=CC=CC=1.[CH2:9]([O:11][C:12](=[O:24])[C:13]([N:21]=[N+]=[N-])=[CH:14][C:15]1[N:16]=[C:17]([Br:20])[S:18][CH:19]=1)[CH3:10]>C(Cl)Cl>[CH2:9]([O:11][C:12]([C:13]1[CH2:14][C:15]2[N:16]=[C:17]([Br:20])[S:18][C:19]=2[N:21]=1)=[O:24])[CH3:10]
Reactant: CCOC(=O)C(=Cc1csc(Br)n1)N=[N+]=[N-]
Solvent: ClCCl
Solvent: Cc1ccccc1C
Product: CCOC(=O)C1=Nc2sc(Br)nc2C1
Temperature: 25 °C
Yield: 25.4 %

Procedure:
Add dropwise to hot xylene (130° C., 4 ml) a solution of 2-azido-3-(2-bromo-4-thiazolyl)propenoic acid ethyl ester (60 mg, 0.2 mmol) in DCM (1 ml). Heat the mixture for one hour, then cool to room temperature, deposit the mixture on a pad of silica gel and elute with heptane:DCM (50%-100%) to provide the title compound (14 mg).
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]1[C@H:10]([C:11]2[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=2[F:19])[CH2:9][C:8](=[O:20])[NH:7][CH2:6]1)=[O:4].[CH3:21][O:22][C:23]1[CH:38]=[CH:37][C:26]([CH:27](O)[C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)=[CH:25][CH:24]=1.S(=O)(=O)(O)O>C(O)(=O)C>[CH3:1][O:2][C:3]([C@H:5]1[C@H:10]([C:11]2[CH:16]=[C:15]([F:17])[C:14]([F:18])=[CH:13][C:12]=2[F:19])[CH2:9][C:8](=[O:20])[N:7]([CH:27]([C:26]2[CH:37]=[CH:38][C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)[C:28]2[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[CH2:6]1)=[O:4]
Reactant: COc1ccc(C(O)c2ccc(OC)cc2)cc1
Reactant: COC(=O)[C@@H]1CNC(=O)C[C@H]1c1cc(F)c(F)cc1F
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: COC(=O)[C@@H]1CN(C(c2ccc(OC)cc2)c2ccc(OC)cc2)C(=O)C[C@H]1c1cc(F)c(F)cc1F
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 6.6 g (23 mmol) of the product of Step C in 100 mL of acetic acid was added 6.11 g (25 mmol) of 4,4′-dimethoxybenzhydrol followed by 5 mL of concentrated sulfuric acid and the resulting solution was stirred at ambient temperature for 18 h. The solution was then concentrated and cooled 0° C. before quenching with ice water (100 mL). The resulting mixture was extracted with three 300-mL portions of ethyl acetate, and the organic phases combined and washed sequentially with water, saturated aqueous sodium bicarbonate solution, and saturated aqueous brine (200 mL each). The organic phase was dried over magnesium sulfate, filtered, and evaporated in vacuo to yield a viscous oil. The crude material was purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 50% ethyl acetate/hexanes gradient) to give methyl-trans-1-[bis(4-methoxyphenyl)methyl]-6-oxo-4-(2,4,5-trifluorophenyl)piperidine-3-carboxylate as a colorless solid. LC/MS 536.2 (M+23).
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:11]1[C:39]([CH3:40])=[CH:38][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:24]4[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[C@H:26]([CH3:37])[CH2:25]4)[N:19]=3)[S:17][C:13]=2[C:12]=1[C:41]1[CH:46]=[CH:45][C:44]([Cl:47])=[CH:43][CH:42]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:4])([CH3:3])[CH3:2].Cl>O1CCOCC1>[C:1]([O:5][C@@H:6]([C:11]1[C:39]([CH3:40])=[CH:38][C:14]2[N:15]=[C:16]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([N:24]4[CH2:29][CH2:28][NH:27][C@H:26]([CH3:37])[CH2:25]4)[N:19]=3)[S:17][C:13]=2[C:12]=1[C:41]1[CH:42]=[CH:43][C:44]([Cl:47])=[CH:45][CH:46]=1)[C:7]([O:9][CH3:10])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(N4CCN(C(=O)OC(C)(C)C)[C@H](C)C4)n3)sc2c1-c1ccc(Cl)cc1
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3ccnc(N4CCN[C@H](C)C4)n3)sc2c1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To crude (R)-tert-butyl 4-(4-(6-((S)-1-tert-butoxy-2-methoxy-2-oxoethyl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-2-yl)pyrimidin-2-yl)-2-methylpiperazine-1-carboxylate in 1,4-dioxane (1.25 mL) was added HCl (0.78 mL of a 4M solution in 1,4-dioxane). The reaction mixture was stirred at room temperature for 2.5 h then concentrated. The resulting solid was suspended in diethyl ether, concentrated and dried under high vacuum overnight. The resulting solid was taken up in water, basified with 2N NaOH, and extracted three times with DCM. The combined organic layers were dried over sodium sulfate, filtered, concentrated, and used without further purification. LCMS-ESI+ calc'd for C30H35ClN5O3S (M+H+): 580.2; Found: 580.2 (M+H+).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([N:16]2[CH2:20][C@@H:19]([N:21]([C:25]([O:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)=[O:26])[CH:22]([CH3:24])[CH3:23])[C@H:18]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)[CH2:17]2)=[O:15])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>>[F:34][C:31]1[CH:32]=[CH:33][C:28]([O:27][C:25](=[O:26])[N:21]([C@H:19]2[C@H:18]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)[CH2:17][N:16]([C:14]([CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[O:15])[CH2:20]2)[CH:22]([CH3:23])[CH3:24])=[CH:29][CH:30]=1
Reactant: CC(C)N(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(C(=O)C2CCN(C(=O)OC(C)(C)C)CC2)C[C@H]1c1ccc(Cl)cc1
Solvent: O=C(O)C(F)(F)F
Product: CC(C)N(C(=O)Oc1ccc(F)cc1)[C@@H]1CN(C(=O)C2CCNCC2)C[C@H]1c1ccc(Cl)cc1

Procedure:
In analogy to the procedure described for the synthesis of [(3R,4S)-4-(4-Chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-ethyl-carbamic acid 4-fluoro-phenyl ester the title compound was prepared from 4-{(3R,4S)-3-(4-Chloro-phenyl)-4-[(4-fluoro-phenoxycarbonyl)-isopropyl-amino]-pyrrolidine-1-carbonyl}-piperidine-1-carboxylic acid tert-butyl ester through cleavage of the protecting group with TFA. The title compound was obtained as off-white foam. MS m/e: 488.3 [M+H]+.
Reaction SMILES: [C:1](Cl)(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[N+:13]([C:16]1[CH:42]=[CH:41][C:19]([CH2:20][O:21][C:22]2[CH:23]=[C:24]([CH:38]=[CH:39][CH:40]=2)[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34](=[O:37])(=[O:36])[NH2:35])=[O:26])=[CH:18][CH:17]=1)([O-:15])=[O:14]>CN(C)C1C=CN=CC=1.O1CCCC1>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([CH2:20][O:21][C:22]2[CH:23]=[C:24]([CH:38]=[CH:39][CH:40]=2)[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34]([NH:35][C:1](=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])(=[O:36])=[O:37])=[O:26])=[CH:41][CH:42]=1)([O-:15])=[O:14]
Reactant: NS(=O)(=O)c1ccccc1NC(=O)c1cccc(OCc2ccc([N+](=O)[O-])cc2)c1
Reactant: CCCCCCCCCC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CCCCCCCCCC(=O)NS(=O)(=O)c1ccccc1NC(=O)c1cccc(OCc2ccc([N+](=O)[O-])cc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.2 %

Procedure:
In a stream of nitrogen and at 0° C., 0.16 ml (0.80 mmol) of decanoyl chloride was added to an anhydrous tetrahydrofuran (10 ml) solution containing 300 mg (0.70 mmol) of 3-(4-nitrobenzyloxy)-N-(2-sulfamoylphenyl)benzamide produced in Reference Example 5 and 171 mg (1.40 mmol) of 4-dimethylaminopyridine, the mixture was stirred at room temperature for 1 hour and then the solvent was evaporated under a reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with water, a potassium hydrgensulfate aqueous solution and saturated brine in that order and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was purified by a silica gel column chromatography to obtain 400 mg (yield: 97.9%) of the title compound.
Reaction SMILES: [O-2:1].[Al+3:2].[O-2].[O-2].[Al+3].[Sm:6]>>[O-2:1].[Al+3:2].[O-2:1].[O-2:1].[Al+3:2].[O-2:1].[Sm+3:6].[O-2:1].[O-2:1].[Sm+3:6]
Reactant: [Sm]
Agent: [Al+3]
Agent: [O-2]
Product: [Sm+3]

Procedure:
Aluminum oxide disks (0.9 inch (2.29 cm) in diameter×0.12 inch (0.30 cm) thick) fabricated by the processes described in Example 1 were selected for evaluating the samarium glaze. Calculations were made based on the density of the samarium glaze (3.2 grams per cubic centimeter) and the surface area of the Al2O3 disks to provide the weight of samarium oxide frit (powdered glass) to yield samarium glaze thicknesses on the Al2O3 disks of 0.001 inch (0.025 millimeter), 0.003 inch (0.076 millimeter), 0.005 inch (0.127 millimeter), 0.007 inch (0.178 millimeter) and 0.009 inch (0.229 millimeter). The calculated weight of samarium frit was placed in the center of each disk. The Al2O3 disks with frit were placed in a furnace and heated to 1300° C. for 60 minute time periods. The frit melted, flowed over the top surface of the disks providing a uniform thickness glaze which was very smooth and transparent to the visible light spectrum Subsequent tests of this glaze indicated an extremely strong bond to the Al2O3 substrate by virtue of the nominal 15% porosity of the substrate. Furthermore the very smooth nature of the glaze provided a surface which did not collect dirt or debris and could be wiped clean just like a glass window. Absorption measurements were made on all five disks (0.001 to 0.009 inch or 0.0254 to 0.229 millimeter thicknesses) in an integrating sphere spectrophotometer from 220 nanometers to 2400 nanometers. Absorption was found at precisely 1.06 microns. There was zero absorption for a BaSO4 standard and an uncoated (noglaze) Al2O3 disk. The absorption for the 0.001 inch thick glaze was significant and progressed in textbook fashion as the thickness increased from 0.001 inch (0.025 millimeter), 0.003 inch (0.076 millimeter), 0.005 inch (0.127 millimeter), 0.007 inch (0.178 millimeter) and 0.009 inch (0.229 millimeter).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)[N:5]=[C:4]([C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:32])[CH3:31])=[CH:25][CH:24]=2)[CH:3]=1.[NH2:33][NH2:34]>CN(C)C=O>[NH2:9][C:8]1[C:7]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:12][CH:11]=3)=[N:5][C:4]([C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:30](=[O:32])[CH3:31])=[CH:25][CH:24]=3)=[CH:3][C:2]=2[NH:34][N:33]=1
Reactant: CC(=O)Nc1ccc(-c2cc(Cl)c(C#N)c(-c3ccc(Oc4ccccc4)cc3)n2)cc1
Reactant: NN
Solvent: CN(C)C=O
Product: CC(=O)Nc1ccc(-c2cc3[nH]nc(N)c3c(-c3ccc(Oc4ccccc4)cc3)n2)cc1
Temperature: 120 °C

Procedure:
A mixture of N-(4-(4-chloro-5-cyano-6-(4-phenoxyphenyl)pyridin-2-yl)phenyl)acetamide (24.9 mg, 0.057 mmol), 35% aqueous hydrazine (20 μL, 0.637 mmol) and N,N-dimethylformamide (0.5 mL) in a sealed tube was heated to 100° C. for 3 h, 120° C. for 6 h and concentrated. Silica gel chromatography, eluting with 0-10% methanol in dichloromethane, gave the desired product. The material was triturated with dichloromethane and filtered to give Example 200 as light yellow solid (9.4 mg, 38% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.20 (1H, s), 10.08 (1H, s), 8.11 (2H, δ, J=8.78 Hz), 7.81-7.84 (2H, m), 7.69 (2H, δ, J=8.78 Hz), 7.63 (1H, s), 7.43-7.48 (2H, m), 7.13-7.23 (5H, m), 4.83 (2H, s), 2.07 (3H, s); MS (ES+) m/z: 436 (M+H); LC retention time: 3.200 min (analytical HPLC Method A).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[N:19]=[C:18]([NH:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([C:27](O)=[O:28])[CH2:23][CH2:22]4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.[CH3:59][N:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[N:19]=[C:18]([NH:20][CH:21]4[CH2:26][CH2:25][CH:24]([C:27]([N:63]5[CH2:64][CH2:65][N:60]([CH3:59])[CH2:61][CH2:62]5)=[O:28])[CH2:23][CH2:22]4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CN1CCNCC1
Reactant: O=C(O)[C@H]1CC[C@H](Nc2ncc3ncnc(Nc4ccc(F)c(Cl)c4)c3n2)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CO
Product: CN1CCN(C(=O)C2CCC(Nc3ncc4ncnc(Nc5ccc(F)c(Cl)c5)c4n3)CC2)CC1

Procedure:
Prepared from 4-[(3-chloro-4-fluorop henyl)amino]-6-[trans-4-carboxycyclohexylamino]pyrimido[5,4-d]pyrimidine by reaction with O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate, triethylamine and 1-methylpiperazine. Melting point: 194°-197° C.; Rf : 0.45 (alumina; methylene chloride/methanol=10:0.3)
Reaction SMILES: [CH:1]1([C:4]([C:6]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[NH:16][C@H:17]2[CH2:22][CH2:21][C@H:20]([NH:23]C(=O)OC(C)(C)C)[CH2:19][CH2:18]2)=[CH:13][C:12]([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[C:33]([O:38][CH3:39])[CH:32]=2)=[CH:11][CH:10]=3)=[O:5])[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>>[NH2:23][C@H:20]1[CH2:21][CH2:22][C@H:17]([NH:16][C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:31]4[CH:36]=[CH:35][C:34]([OH:37])=[C:33]([O:38][CH3:39])[CH:32]=4)[CH:13]=3)[N:8]=[CH:7][C:6]=2[C:4]([CH:1]2[CH2:2][CH2:3]2)=[O:5])[CH2:18][CH2:19]1
Reactant: COc1cc(-c2ccc3ncc(C(=O)C4CC4)c(N[C@H]4CC[C@H](NC(=O)OC(C)(C)C)CC4)c3c2)ccc1O
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(-c2ccc3ncc(C(=O)C4CC4)c(N[C@H]4CC[C@H](N)CC4)c3c2)ccc1O

Procedure:
Following general procedure A-2, tert-butyl trans-4-[3-(cyclopropanecarbonyl)-6-(4-hydroxy-3-methoxyphenyl)quinolin-4-ylamino]cyclohexylcarbamate (45 mg, 0.085 mmol) was reacted with TFA (2 mL) to afford the desired product (11.3 mg, 31%) as a yellow solid: 1H NMR (500 MHz, CD3OD) δ 9.12 (s, 1H), 8.36 (s, 1H), 8.04-7.98 (m, 1H), 7.89 (d, J=8.7 Hz, 1H), 7.26 (d, J=1.9 Hz, 1H), 7.17 (dd, J=8.2, 2.0 Hz, 1H), 6.93 (d, J=8.2 Hz, 1H), 4.14 (s, 1H), 3.97 (s, 3H), 3.20-3.07 (m, 2H), 2.87-2.75 (m, 2H), 2.28 (d, J=12.2 Hz, 2H), 2.01 (d, J=11.6 Hz, 2H), 1.64-1.53 (m, 2H), 1.40-1.26 (m, 3H), 1.21-1.14 (m, 2H), 1.12-1.03 (m, 2H); ESI MS m/z 432 [C26H29N3O3+H]+; HPLC 98.8% (AUC), tR=7.95 min.
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C:3]#[C:4][CH2:5][CH2:6]O.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:22][NH:23][CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1>CN(C)C=O>[CH3:22][N:23]([CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)[CH2:6][CH2:5][C:4]#[C:3][C:2]([CH3:9])([CH3:8])[CH3:1]
Reactant: CC(C)(C)C#CCCO
Reactant: CNCc1cccc2ccccc12
Agent: CS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN(CCC#CC(C)(C)C)Cc1cccc2ccccc12

Procedure:
To a solution of 540 mg 5,5-dimethyl-3-hexyn-1-ol in dimethylformamide (DMF) are added, at 0° 1.2 ml triethylamine. Then are added, dropwise, with stirring, 0.335 ml methanesulfonylchloride. After 2 hours of stirring at room temperature are added 740 mg N-methyl-1-naphthylmethylamine and the mixture is heated overnight at 80°. The solvent is evaporated in vacuum, the residue distributed between saturated aqueous NaHCO3 solution and ethyl acetate, the organic phase washed, dried and evaporated. The crude residue is chromatographed over silicagel (with toluene/ethylacetate 9/1) and the title compound (Compound 1) obtained as an oil.