Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:26])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][NH:9][C:10](=[O:25])[CH:11]=[C:12]1[C:24]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[C:18]2[C:13]1=[CH:14][CH:15]=[CH:16][CH:17]=2.CO.[Li+].[OH-].Cl>O>[CH:14]1[C:13]2[C:12](=[CH:11][C:10]([NH:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:26])=[O:2])=[O:25])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:18]=2[CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)CCCCCNC(=O)C=C1c2ccccc2-c2ccccc21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CCCCCNC(=O)C=C1c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 24 h
Yield: 83.8 %

Procedure:
6-(2-(9H-fluoren-9-ylidene)acetamido)hexanoic acid methyl ester (349 mg, 1 mmol) and 300 ml of CH3OH were stirred at room temperature while 25 ml of 4 N solution of LiOH in H2O was added. The mixture was stirred for 24 hours at room temperature. The mixture was neutralized with concentrated hydrochloric acid to pH 7 and evaporated under vacuum to remove methanol. The residue was adjusted to pH 3 with concentrated hydrochloric acid. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (281 mg, 84% yield) as a white solid. 1H NMR (DMSO-d6) δ1.30 (m, 2H, CH2), 1.51 (m, 4H, 2×CH2), 2.18 (t, J=8.0 Hz, 2H, CH2CO), 3.23 (m, 2H, NCH2), 7.08 (s, 1H, ═CH—CO), 7.34 (m, 2H, Ar—H), 7.41 (t, J=8.0 Hz, 2H, Ar—H), 7.76 (d, J=8.0 Hz, 1H, Ar—H), 7.81 (m, 2H, Ar—H), 8.53 (t, J=4.0 Hz, 1H, CONH), 8.68 (d, J=8.0 Hz, 1H, Ar—H). LC-MS (m/z) 336 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH2:15][C:14]([CH3:25])([CH3:24])[C:13]=2[CH:12]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][CH2:33][N:34]1[C:38](=[O:39])[CH2:37][S:36][C:35]1=[O:40]>>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[C:37]2[S:36][C:35](=[O:40])[N:34]([CH2:33][CH2:32][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=3)[C:38]2=[O:39])=[CH:5][C:4]=1[C:11]1[C:20]([CH3:21])=[CH:19][C:18]2[C:17]([CH3:23])([CH3:22])[CH2:16][CH2:15][C:14]([CH3:25])([CH3:24])[C:13]=2[CH:12]=1
Reactant: O=C1CSC(=O)N1CCc1ccccn1
Reactant: COc1ccc(C=O)cc1-c1cc2c(cc1C)C(C)(C)CCC2(C)C
Product: COc1ccc(C=C2SC(=O)N(CCc3ccccn3)C2=O)cc1-c1cc2c(cc1C)C(C)(C)CCC2(C)C

Procedure:
5-[4-Methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-benzylidene]-3-(2-pyridin-2-yl-ethyl)-thiazolidine-2,4-dione was prepared in a similar manner as described in Example 1 using 4-methoxy-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl) benzaldehyde and 3-(2-pyridin-2-yl-ethyl)-thiazolidine-2,4-dione, mp 170–171° C., 1H NMR (300 MHz; DMSO-d6) 1.23 (s, 6 H); 1.28 (s, 6 H); 1.65 (s, 4 H); 2.02 (s, 3 H); 3.04 (t, J=7.1 Hz, 2 H); 3.81 (s, 3 H); 3.99 (t, J=7.1 Hz, 2 H); 7.04 (s, 1 H); 7.18–7.29 (m, 4 H); 7.36 (d, J=2.1 Hz, 1 H); 7.64 (dd, J1=9 Hz, J2=3.6 Hz, 1 H); 7.70 (t, J=3.7 Hz, 1 H); 7.91 (s, 1 H); 8.46 (d, J=4.0 Hz, 1 H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([NH:12][NH2:13])=[O:11])[CH:5]=[CH:6][CH:7]=1.[NH:14]1[C:18]2[N:19]=[CH:20][CH:21]=[C:22]([C:23](O)=O)[C:17]=2[CH:16]=[CH:15]1>>[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[O:11][C:23]([C:22]3[CH:21]=[CH:20][N:19]=[C:18]4[NH:14][CH:15]=[CH:16][C:17]=34)=[N:13][N:12]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: NNC(=O)CCc1cccc(F)c1
Reactant: O=C(O)c1ccnc2[nH]ccc12
Product: Fc1cccc(CCc2nnc(-c3ccnc4[nH]ccc34)o2)c1
Yield: 40 %

Procedure:
In the same manner as in Example 14 and using 3-(3-fluorophenyl)propanohydrazide instead of 1H-benzotriazole-5-carbohydrazide and 1H-pyrrolo[2,3-b]pyridine-4-carboxylic acid instead of 3-(3-cyanophenyl)propionic acid, the title compound (yield 40%) was obtained as pale-yellow crystals.
Reaction SMILES: [N:1]1([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20](Cl)[N:19]=4)=[N:16][N:17]=3)[N:14]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:25][O-:26].[Na+]>C1(C)C=CC=CC=1>[N:1]1([C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([O:26][CH3:25])[N:19]=4)=[N:16][N:17]=3)[N:14]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C[O-]
Reactant: Clc1cccc(-c2nnc3ccc(N4CCCCCCC4)nn23)n1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1cccc(-c2nnc3ccc(N4CCCCCCC4)nn23)n1
Temperature: 25 °C
Yield: 81.6 %

Procedure:
A mixture of 6-azocan-1-yl-3-(6-chloropyridin-2-yl)-1,2,4-triazolo[4,3-b]pyridazine (360 mg), sodium methoxide (570 mg) and toluene (20 ml) was stirred with heating under reflux for 3 hours. After allowing to cool to room temperature, the reaction solution was concentrated under reduced pressure, and the resultant residue was extracted with ethyl acetate. The extract was washed with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant crude crystal was washed with diethyl ether to obtain 6-azocan-1-yl-3-(6-methoxypyridin-2-yl)-1,2,4-triazolo[4,3-b]pyridazine (290 mg) as pale yellow crystals.
Reaction SMILES: [CH2:1]1[C@@H:5]([C:6]([OH:8])=[O:7])[NH:4][CH2:3][C@H:2]1[OH:9].[OH2:10]>>[OH:9][C@H:2]([CH2:3][OH:10])[CH2:1][C@@H:5]([C:6]([OH:8])=[O:7])[NH2:4]
Reactant: O
Reactant: O=C(O)[C@@H]1C[C@H](O)CN1
Product: N[C@@H](C[C@H](O)CO)C(=O)O

Procedure:
[α]D21 =-23.9 (c =1.0, water) Further reactions analogously to J. Am. Chem. Soc. 1986, 108, 6041 lead to L-cis-4-hydroxyproline
Reaction SMILES: [O:1]=[C:2]1[N:7]2[CH:8]=[C:9]([C:12]#[N:13])[CH:10]=[CH:11][C:6]2=[N:5][C:4]2[CH2:14][S:15][CH2:16][C:3]1=2.[N-:17]=[N+:18]=[N-:19].[Na+].[Cl-].[NH4+]>CN(C)C=O>[O:1]=[C:2]1[N:7]2[CH:8]=[C:9]([C:12]3[NH:19][N:18]=[N:17][N:13]=3)[CH:10]=[CH:11][C:6]2=[N:5][C:4]2[CH2:14][S:15][CH2:16][C:3]1=2
Reactant: N#Cc1ccc2nc3c(c(=O)n2c1)CSC3
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=c1c2c(nc3ccc(-c4nnn[nH]4)cn13)CSC2

Procedure:
A mixture of 3,10-dihydro-10-oxo-1H-pyrido[1,2-a]thieno[3,4-d]pyrimidine-7-carbonitrile (1.0 g., 0.004 mol), sodium azide (0.81 g., 0.012 mol) and ammonium chloride (0.69 g., 0.013 mol) in dimethylformamide (150 ml) is heated at 100°-105° C. for 18 hours. The solvent is removed at reduced pressure. The residue is triturated with 1 N hydrochloric acid, filtered, washed with water, dissolved in 10% aqueous potassium carbonate, filtered and reprecipitated with 1 N hydrochloric acid. The solid is filtered off and recrystallized from dimethylformamide-methanol to give a crystalline product (0.96 g.), mp 285° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][CH2:14][NH:15][C:16]([NH:18][CH2:19][CH2:20][CH3:21])=[O:17])=[CH:9][CH:8]=[C:7]([Br:22])[CH:6]=2.[CH2:23]([O:25][CH2:26][C:27](Cl)=O)[CH3:24]>N1C=CC=CC=1>[Br:22][C:7]1[CH:8]=[CH:9][C:10]2[C:11]3[N:12]([CH2:13][CH2:14][NH:15][C:16]([NH:18][CH2:19][CH2:20][CH3:21])=[O:17])[C:24]([CH2:23][O:25][CH2:26][CH3:27])=[N:1][C:2]=3[CH:3]=[N:4][C:5]=2[CH:6]=1
Reactant: CCCNC(=O)NCCNc1c(N)cnc2cc(Br)ccc12
Reactant: CCOCC(=O)Cl
Solvent: c1ccncc1
Product: CCCNC(=O)NCCn1c(COCC)nc2cnc3cc(Br)ccc3c21
Temperature: 80 °C
Reaction time: 1.5 h

Procedure:
To a stirred solution of 1-[2-(3-amino-7-bromoquinolin-4-ylamino)ethyl]-3-(2-methylethyl)urea (27.2 g, 0.0743 mol) in 600 mL pyridine was slowly added ethoxyacetyl chloride (1.1 equivalents). After 1.5 hours the mixture was yellow and turbid. The reaction mixture was then heated at 80° C. for 12 hours and then concentrated under reduced pressure. The residue was dissolved in water and saturated aqueous potassium carbonate and stirred vigorously for three hours. A precipitate was present, was isolated by filtration, and air-dried for 48 hours to provide 32 g of 1-[2-(7-bromo-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl)ethyl]-3-(2-methylethyl)urea.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][OH:12])=[CH:7][C:6]=1[NH:13][C:14](=[O:30])[CH2:15][CH:16]1[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[O:23][C:22]2[C:17]1=[CH:18][CH:19]=[CH:20][CH:21]=2)([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(OCC)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[CH:7][C:6]=1[NH:13][C:14](=[O:30])[CH2:15][CH:16]1[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=2[O:23][C:24]2[C:29]1=[CH:28][CH:27]=[CH:26][CH:25]=2)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(CO)cc1NC(=O)CC1c2ccccc2Oc2ccccc21
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)(C)c1ccc(C=O)cc1NC(=O)CC1c2ccccc2Oc2ccccc21
Reaction time: 1.75 h
Yield: 88 %

Procedure:
1.24 g (3.08 mmol) of N-(2-t-butyl-5-hydroxymethyl-phenyl)-2-(9H-xanthen-9-yl)acetamide (prepared as described in Preparation 14) were added to 12 ml of a methylene chloride suspension containing 1.06 g (4.92 mmol) of pyridinium chlorochromate. The mixture was then stirred for 1.75 hours. At the end of this time, the reaction suspension was diluted with diethyl ether, filtered through a column using 50 ml of Florisil (trade mark) absorbent, and eluted with a 1:1 by volume mixture of methylene chloride and diethyl ether. The solvent was then removed by distillation under reduced pressure. The resulting residue was subjected to column chromatography through 50 g of silica gel. Elution with a 1:9 by volume mixture of diethyl ether and methylene chloride afforded the title compound containing a small amount of impurities. Recrystallization of this from a mixture of ethyl acetate and hexane afforded 442 mg of the title compound as crystals, melting at 172.5°-174° C. (after recrystallization from a mixture of ethyl acetate and hexane). The mother liquors were condensed and subjected to column chromatography through 100 g of silica gel. Elution with a 4:6 by volume mixture of ethyl acetate and hexane afforded a further 643 mg of the title compound. The total yield was 88%.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[C:34]([OH:37])(=[S:36])[CH3:35].[C:38]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]([CH2:66][C:67]2[CH:72]=[CH:71][C:70]([O:73][CH2:74][CH2:75]O)=[CH:69][CH:68]=2)[C:49]([NH:51][C:52]2[CH:57]=[CH:56][C:55]([O:58][CH2:59][CH:60]3[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]3)=[CH:54][CH:53]=2)=[O:50])=[CH:44][CH:43]=1)([CH3:41])([CH3:40])[CH3:39]>C1COCC1>[C:38]([C:42]1[CH:43]=[CH:44][C:45]([CH:48]([C:49](=[O:50])[NH:51][C:52]2[CH:53]=[CH:54][C:55]([O:58][CH2:59][CH:60]3[CH2:65][CH2:64][CH2:63][CH2:62][CH2:61]3)=[CH:56][CH:57]=2)[CH2:66][C:67]2[CH:72]=[CH:71][C:70]([O:73][CH2:74][CH2:75][S:36][C:34](=[O:37])[CH3:35])=[CH:69][CH:68]=2)=[CH:46][CH:47]=1)([CH3:39])([CH3:40])[CH3:41]
Reactant: CC(C)(C)c1ccc(C(Cc2ccc(OCCO)cc2)C(=O)Nc2ccc(OCC3CCCCC3)cc2)cc1
Reactant: CC(O)=S
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(=O)SCCOc1ccc(CC(C(=O)Nc2ccc(OCC3CCCCC3)cc2)c2ccc(C(C)(C)C)cc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75.4 %

Procedure:
To a solution of triphenylphosphine (125 mg, 0.48 mmol) in anhydrous THF (5 mL) at 0° C. was added diisopropylazodicarboxylate (94 uL, 0.48 mmol). After stirring for 30 min. a solution consisting of thioacetic acid (34 uL, 0.48 mmol) and 2-(4-tert-Butylphenyl)-N-(4-cyclohexylmethoxyphenyl)-3-[4-(2-hydroxyethoxy)-phenyl]-propionamide (126 mg, 0.23 mmol) was added. The resulting solution was allowed to warm to rt overnight. The mixture was partitioned between ethyl acetate and H2O and the organic portion concentrated under vacuum. Purification of the crude by preparative TLC (SiO2, 2 mm) using hexane/ethyl acetate (4:1) as eluant afforded Thioacetic acid S-(2-{4-[2-(4-tert-Butylphenyl)-2-(4-cyclohexylmethoxyphenyl carbamoyl)-ethyl]-phenoxy}-ethyl)ester (102 mg, 73%). TLC: Rf=0.38 hexane/ethyl acetate (4:1).
Reaction SMILES: [H-].[Na+].[N:3]1([C:10]2[C:19]3[C:14](=[CH:15][C:16]([CH2:20][OH:21])=[CH:17][CH:18]=3)[N:13]=[C:12]([CH3:22])[CH:11]=2)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.F[C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=1>CN(C)C=O>[N:3]1([C:10]2[C:19]3[C:14](=[CH:15][C:16]([CH2:20][O:21][C:24]4[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][CH:25]=4)=[CH:17][CH:18]=3)[N:13]=[C:12]([CH3:22])[CH:11]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]1
Reactant: N#Cc1ccc(F)cc1
Reactant: Cc1cc(N2CCCCCC2)c2ccc(CO)cc2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(N2CCCCCC2)c2ccc(COc3ccc(C#N)cc3)cc2n1
Temperature: 50 °C
Yield: 88.1 %

Procedure:
Sodium hydride (55–65% dispersion in mineral oil, 22 mg, 0.55 mmol) was added to a mixture of (4-azepan-1-yl-2-methyl-quinolin-7-yl)-methanol (example 3, 120 mg, 0.44 mmol) and 4-fluorobenzonitrile (54 mg, 0.44 mmol) in N,N-dimethylformamide (1.5 mL). After heating 2 h at 50° C., the reaction mixture was partitioned between sat. aq. ammonium chloride solution and dichloromethane. The organic layer was separated, washed with brine, dried (MgSO4), and evaporated. Chromatography (SiO2, CH2Cl2/MeOH 95:5) yielded the title compound (144 mg, 87%). Light yellow solid, ISP-MS: m/e=372.3 ([M+H]+).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[C:11]1([C:2]2[CH:7]=[C:6]([CH:5]=[CH:4][N:3]=2)[C:8]([OH:10])=[O:9])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(O)c1ccnc(Br)c1
Reactant: OB(O)c1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(O)c1ccnc(-c2ccccc2)c1
Temperature: 150 °C
Yield: 53 %

Procedure:
A mixture of 2-bromo-4-pyridinecarboxylic acid (1.1 g, 5.45 mmol), phenylboronic acid (1.3 g, 10.9 mmol), 2.0 M potassium phosphate (aq) (8.2 mL, 16.34 mmol), and DMF (10 mL) in a 20 mL microwave tube was degassed under vacuum/Ar. A catalytic amount of tetrakis(triphenylphosphine)palladium(0) was added to the tube, the mixture was degassed again, the tube was sealed, and the reaction was heated at 150° C. in the microwave for 30 min. The reaction mixture was filtered, the filtrate was concentrated in-vacuo, and the residue was dissolved in water (10 mL). The mixture was acidified to pH=6 with the addition of 1.0 N HCl, and the resulting precipitate was collected by filtration, rinsed with two portions of ice-cold water, and air dried to yield 575 mg of 2-phenylisonicotinic acid as an off-white solid. MS (ES+)=200 (M+H+).
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@H:9]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]([Cl:17])[CH:11]=2)[O:8][CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:4]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:32]1[N:41]=[CH:40][CH:39]=[CH:38][C:33]=1[C:34]([O:36][CH3:37])=[O:35]>CN(C=O)C.C(OCC)(=O)C>[Cl:17][C:12]1[CH:11]=[C:10]([C@@H:9]2[O:8][CH2:7][CH2:6][N:5]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:4][C@H:3]2[CH2:2][NH:1][C:32]2[C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:38][CH:39]=[CH:40][N:41]=2)[CH:15]=[CH:14][C:13]=1[Cl:16]
Reactant: CC(C)(C)OC(=O)N1CCO[C@@H](c2ccc(Cl)c(Cl)c2)[C@H](CN)C1
Reactant: COC(=O)c1cccnc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cccnc1NC[C@@H]1CN(C(=O)OC(C)(C)C)CCO[C@H]1c1ccc(Cl)c(Cl)c1
Temperature: 100 °C
Reaction time: 48 h
Yield: 44.1 %

Procedure:
To a solution of tert-butyl (6R,7R)-6-(aminomethyl)-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate (200 mg) in DMF (4 mL) were added potassium carbonate (110 mg) and methyl 2-chloronicotinate (137 mg) at room temperature, and the mixture was stirred at 100° C. for 48 hr. The reaction mixture was diluted with ethyl acetate. The diluted solution was washed with distilled water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (120 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([F:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([Si](C)(C)C)=[CH:20][C:19]=1[F:28])=[O:5])[CH3:2].[I:29]Cl>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:14]([CH3:15])[C:13]2[C:12]([F:16])=[CH:11][N:10]=[CH:9][C:8]=2[C:7]=1[NH:17][C:18]1[CH:23]=[CH:22][C:21]([I:29])=[CH:20][C:19]=1[F:28])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(Nc2ccc([Si](C)(C)C)cc2F)c2cncc(F)c2n1C
Reactant: ClI
Solvent: ClCCl
Product: CCOC(=O)c1c(Nc2ccc(I)cc2F)c2cncc(F)c2n1C
Reaction time: 0.5 h
Yield: 71 %

Procedure:
To a cooled (0° C.) solution of 7-fluoro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid ethyl ester (1.0 g, 2.48 mmol) in DCM (25 mL) was added iodine monochloride (1M in DCM, 4.96 mmol, 4.96 mL) dropwise. The mixture was stirred cold for 30 minutes then quenched by the addition of a saturated solution of sodium thiosulphate. The organic layer was separated, washed with a saturated solution of sodium thiosulphate, then dried (Na2SO4), filtered and evaporated to give a residue. The residue was triturated with diethyl ether to provide the title compound as a beige solid (805 mg, 71%). LCMS (method B): RT=3.52 min, M+H+ 458.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[C:21](=[O:33])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH:23]=[CH:24][CH:25]=1>ClCCl.CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([NH:19][C:20]1[C:21](=[O:33])[N:22]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH:23]=[CH:24][CH:25]=1)=[O:6]
Reactant: O=C(O)c1cc(F)c(F)cc1F
Reactant: Nc1cccn(-c2ccc(F)cc2)c1=O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Nc1cccn(-c2ccc(F)cc2)c1=O)c1cc(F)c(F)cc1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 66.8 %

Procedure:
To a solution of 2,4,5-trifluorobenzoic acid (Aldrich, 704 mg, 4.0 mmol) in dichloromethane (20 mL), was added oxalyl chloride (Aldrich, 0.70 mL, 8.0 mmol) dropwise, followed by two drops of DMF. The reaction mixture was stirred at room temperature for 2 h, and concentrated in vacuo. Toluene (20 mL) was added and the reaction mixture was evaporated in vacuo to remove the excess oxalyl chloride. The residue was dissolved in dichloromethane (20 mL). Half of this acid chloride solution was added to a mixture of 3-amino-1-(4-fluorophenyl)pyridin-2(1H)-one (306 mg, 1.5 mmol) in dichloromethane (5 mL) and TEA (0.5 mL, Aldrich) at 0° C. The reaction mixture was stirred at room temperature for 1 h. The precipitate that formed was collected by filtration, and washed with methanol, to afford the desired product (363 mg, 67% yield) as a solid. MS(ESI+) m/z 363.25 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[S:19]([CH3:22])(=[O:21])=[O:20])[C:3]=1[CH3:23].[Br:24][C:25]1[CH:26]=[C:27]2[NH:33][CH2:32][C:31]([CH3:35])([CH3:34])[C:28]2=[N:29][CH:30]=1.Cl.O1CCOCC1>CN1C(=O)CCC1>[Br:24][C:25]1[CH:26]=[C:27]2[N:33]([C:2]3[C:11]4[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=4)[N:5]=[C:4]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=4[S:19]([CH3:22])(=[O:21])=[O:20])[C:3]=3[CH3:23])[CH2:32][C:31]([CH3:35])([CH3:34])[C:28]2=[N:29][CH:30]=1
Reactant: Cc1c(-c2ccccc2S(C)(=O)=O)nc2cc(F)ccc2c1Cl
Reactant: CC1(C)CNc2cc(Br)cnc21
Agent: Cl
Solvent: C1COCCO1
Solvent: CN1CCCC1=O
Product: Cc1c(-c2ccccc2S(C)(=O)=O)nc2cc(F)ccc2c1N1CC(C)(C)c2ncc(Br)cc21
Temperature: 150 °C

Procedure:
Prepared according to procedure L using 4-chloro-7-fluoro-3-methyl-2-(2-(methylsulfonyl)phenyl)quinoline (242 mg, 0.69 mmol) (described herein), 6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridine (157 mg, 0.69 mmol) (described herein), 4.0 M hydrochloric acid in 1,4-dioxane (0.17 mL, 0.69 mmol), and NMP (1.2 mL). The reaction mixture was stirred and heated in a microwave at 150° C. for 120 min. Chromatography afforded 4-(6-bromo-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-7-fluoro-3-methyl-2-(2-(methylsulfonyl)-phenyl)quinoline as a dark oil. Mass Spectrum (ESI) m/e=541 (M+1).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH:7]=O.[NH2:9][CH2:10][C:11]1[CH:38]=[CH:37][C:14]([CH2:15][N:16]([CH2:27][C:28]2[NH:32][C:31]3[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=3[N:29]=2)[CH:17]2[C:26]3[N:25]=[CH:24][CH:23]=[CH:22][C:21]=3[CH2:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[BH4-].[Na+]>CO>[NH:29]1[C:30]2[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=2[N:32]=[C:28]1[CH2:27][N:16]([CH2:15][C:14]1[CH:37]=[CH:38][C:11]([CH2:10][NH:9][CH2:7][C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)=[CH:12][CH:13]=1)[CH:17]1[C:26]2[N:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH2:20][CH2:19][CH2:18]1
Reactant: NCc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Reactant: Cn1ccnc1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cn1ccnc1CNCc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Yield: 67.5 %

Procedure:
Using General Procedure B: A solution of 1-methyl-2-imidazole carboxaldehyde (27.5 mg, 0.25 mmol) and (4-aminomethyl-benzyl)-(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (100 mg, 0.25 mmol) in MeOH (2.0 mL) was stirred overnight at room temperature. NaBH4 (37.5, 0.75 mmol) was added and the resultant mixture stirred for an additional 15 minutes. Purification of the crude white foam by column chromatography on silica gel (CH2Cl2[MeOH/NH4OH, 50:1:1) followed by radial chromatography on silica gel (CH2Cl2/MeOH/NH4OH, 200:3:2) afforded the desired amine (83 mg, 67%) as a white foam.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:19])[S:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=2)(=[O:11])=[O:10])[CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:40]=[CH:39][C:31]3[N:32]=[C:33]([NH:35][C:36](=[O:38])[CH3:37])[S:34][C:30]=3[CH:29]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH3:19][N:8]([C:6]1[N:7]=[C:2]([C:28]2[CH:40]=[CH:39][C:31]3[N:32]=[C:33]([NH:35][C:36](=[O:38])[CH3:37])[S:34][C:30]=3[CH:29]=2)[CH:3]=[CH:4][CH:5]=1)[S:9]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[CH:13]=1)(=[O:11])=[O:10]
Reactant: CC(=O)Nc1nc2ccc(B3OC(C)(C)C(C)(C)O3)cc2s1
Reactant: Cc1cccc(S(=O)(=O)N(C)c2cccc(Cl)n2)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(=O)Nc1nc2ccc(-c3cccc(N(C)S(=O)(=O)c4cccc(C)c4)n3)cc2s1
Temperature: 95 °C
Reaction time: 3 h

Procedure:
N-(6-chloropyridin-2-yl)-N,3-dimethylbenzenesulfonamide (0.200 g, 0.7 mmol) was dissolved in 1,4-dioxane (6 ml), then N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]thiazol-2-yl)acetamide (0.300 g, 1 mmol), tetrakis (triphenylphosphine)palladium(0) (0.100 g, 0.1 mmol) and 2M sodium carbonate (1 ml, 2 mmol) was added to the mixture. The flask was fitted with a reflux condenser and placed into a pre-heated (95° C.) bath. The mixture was allowed to stir under inert atmosphere for 3 hours. The progress of the reaction was monitored by LC/MS, which showed desired product. The mixture was allowed to cool to ambient temperature and diluted with DCM and saturated sodium bicarbonate solution. The organic layer was collected by extracting with DCM (3×20 ml). Combined organic extracts, dried over sodium sulfate, filtered and concentrated in vacuo. The crude was filtered and purified by silica-gel chromatography, in a gradient of 1-10% IPA/DCM over 30 minutes. The fractions with desired product were combined and concentrated. The crude was recrystallized from DCM/Hexanes to give N-(6-(6-(N,3-dimethylphenylsulfonamido)pyridin-2-yl)benzo[d]thiazol-2-yl)acetamide (0.175 g, 57% yield) as a yellow crystalline solid. MS (ESI pos. ion) m/z: 453 (MH+). Calc'd exact mass for C22H20N4O3S2: 452. 1H NMR (400 MHz, DMSO-d6): 2.22 (s, 3H), 2.31 (s, 3H), 3.40 (s, 3H), 7.34-7.56 (m, 5H), 7.75 (d, J=8.53 Hz, 1H), 7.84 (d, J=7.53 Hz, 1H), 7.93 (t, J=6.53 Hz, 2H), 8.40 (s, 1H), 12.42 (s, 1H).