Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH2:7][CH2:8][CH2:9][NH2:10])[CH2:2][CH2:3][CH2:4][CH2:5][NH2:6].[CH2:11]([O:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[O:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH:47]=[CH:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH:33]=O)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[BH4-].[Na+].CCCCCC>C(Cl)Cl.CO>[CH2:11]([O:29][C:30]1[CH:31]=[C:32]([CH:35]=[CH:36][C:37]=1[O:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH:47]=[CH:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH3:56])[CH2:33][NH:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][CH2:7][CH2:8][CH2:9][NH2:10])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH:19]=[CH:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: NCCCCCCCCN
Reactant: CCCCCCCCC=CCCCCCCCCOc1ccc(C=O)cc1OCCCCCCCCC=CCCCCCCCC
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCCCCC
Solvent: ClCCl
Product: CCCCCCCCC=CCCCCCCCCOc1ccc(CNCCCCCCCCN)cc1OCCCCCCCCC=CCCCCCCCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.2 %

Procedure:
To a vigorously stirred solution of diaminooctane (0.23 g, 1.56 mmol, 5 equiv) in CH2Cl2/MeOH (3:1, 5 mL) was added a solution of the aldehyde 8a (0.20 g, 0.33 mmol) in CH2Cl2/MeOH (3:1, 5 mL), dropwise over 1 hour. The resulting mixture was stirred at RT under an atmosphere of nitrogen overnight. NMR showed the reaction to be complete when there was no aldehyde peak present in the NMR spectrum. The solvent was removed in vacuo and the crude imine dissolved in CH2Cl2/MeOH (1:1, 10 mL). The solution was cooled to 0° C. and sodium borohydride (60 mg, 1.58 mmol) was added in 15 mg portions over 30 minutes. TLC (10% EtAc/hexane) showed the reaction to be complete after stirring overnight. The solvent was removed in vacuo and the crude solid dissolved in CH2Cl2 (50 mL) and washed with sodium carbonate (10% aq, 3×40 mL). The CH2Cl2 layer was dried over sodium sulfate, filtered, the solvent removed in vacuo and the solid residue purified by flash column chromatography (1:10:89 NH4OH:MeOH:CHCl3) to give the product 16 as a white solid (0.15 g, 63%), Rf=0.5 (1:10:89 NH4OH:MeOH:CHCl3). 1H NMR (CDCl3) d 6.85 (s, 1H, aryl), 6.80 (m, 2H, aryl), 5.34 (t, 4H, olefinic), 3.97 (q, 4H, OCH2), 3.69 (s, 2H, benzylic), 2.67 (t, 2H, CH2NH2), 2.60 (t, 2H, CH2NH2), 2.01 (m, 8H, CH2C═C), 1.80 (m, 4H, CH2CH2O), 1.54-1.18 (m, 56H, 28×CH2), 0.88 (t, 6H, CH3); 13C NMR (CDCl3) d 149.31, 148.20, 133.55, 130.11, 130.00, 120.59, 114.14, 114.07, 69.70, 69.50, 54.24, 49.83, 42.60, 34.20, 32.28, 30.46, 30.16, 29.92, 29.81, 29.71, 29.67, 27.73, 27.60, 27.22, 26.44, 23.08, 14.53; HRMS (FAB): theory for C51H95N2O2 (M+1), 767.7394; found (M+1), 767.7377. Anal. (C51H94N2O2.0.3H2O): C, H, N.
Reaction SMILES: [I:1][C:2]1[C:19]([O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]([NH:29][CH3:30])=[O:28])=[CH:23][N:22]=2)=[CH:18][C:5]2[CH2:6][CH2:7][N:8](C(OC(C)(C)C)=O)[CH2:9][CH2:10][C:4]=2[CH:3]=1.C(OC1C=CC2CCNCCC=2C=1)C1C=CC=CC=1>>[CH3:30][NH:29][C:27]([C:24]1[CH:23]=[N:22][C:21]([O:20][C:19]2[C:2]([I:1])=[CH:3][C:4]3[CH2:10][CH2:9][NH:8][CH2:7][CH2:6][C:5]=3[CH:18]=2)=[CH:26][CH:25]=1)=[O:28]
Reactant: CNC(=O)c1ccc(Oc2cc3c(cc2I)CCN(C(=O)OC(C)(C)C)CC3)nc1
Agent: c1ccc(COc2ccc3c(c2)CCNCC3)cc1
Product: CNC(=O)c1ccc(Oc2cc3c(cc2I)CCNCC3)nc1

Procedure:
Description 43 (D43) was prepared from 1,1-dimethylethyl 7-iodo-8-({5-[(methylamino)carbonyl]-2-pyridinyl}oxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (D42) using an analogous method to that described for Description 2 (D2); MS (ES+) m/e 424 [M+H]+.
Reaction SMILES: [CH3:1][Mg+].[Br-].[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH2:12][O:13][C@@H:14]1[C@@H:20]([CH2:21][O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])[O:19][C@H:16]([O:17][CH3:18])[C:15]1=[O:32]>CCOCC>[Cl:4][C:5]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:6]=1[CH2:12][O:13][C@@H:14]1[C@@H:20]([CH2:21][O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=2[Cl:31])[O:19][C@H:16]([O:17][CH3:18])[C@:15]1([CH3:1])[OH:32]
Reactant: CO[C@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)C1=O
Reactant: C[Mg+]
Agent: [Br-]
Solvent: CCOCC
Product: CO[C@H]1O[C@H](COCc2ccc(Cl)cc2Cl)[C@@H](OCc2ccc(Cl)cc2Cl)[C@@]1(C)O
Temperature: -30 °C
Reaction time: 7 h

Procedure:
To a solution of MeMgBr in anhydrous Et2O (0.48 M, 300 mL) at −55° C. was added dropwise a solution of the compound from Step B (17.40 g, 36.2 mmol) in anhydrous Et2O (125 mL). The reaction mixture was allowed to warm to −30° C. and stirred for 7 h at −30° C. to −15° C., then poured into ice-cold water (500 mL) and the mixture vigorously stirred at room temperature for 0.5 h. The mixture was filtered through a Celite pad (10×5 cm) which was thoroughly washed with Et2O. The organic layer was dried (MgSO4), filtered and concentrated. The residue was dissolved in hexanes (˜30 mL), applied onto a silica gel column (10×7 cm, prepacked in hexanes) and eluted with hexanes and hexanes/EtOAc (9/1) to give the title compound (16.7 g) as a colorless syrup.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([C:19](=[S:21])[NH2:20])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)(C)(C)C.Br[CH2:24][C:25](=O)[CH2:26][CH3:27].C(OCC)C>CC#N>[CH2:26]([C:25]1[N:20]=[C:19]([C@@H:8]([NH2:7])[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([N+:16]([O-:18])=[O:17])=[CH:14][CH:15]=2)[S:21][CH:24]=1)[CH3:27]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(N)=S
Reactant: CCC(=O)CBr
Solvent: CC#N
Solvent: CCOCC
Product: CCc1csc([C@@H](N)Cc2ccc([N+](=O)[O-])cc2)n1
Temperature: 25 °C
Yield: 90 %

Procedure:
A mixture of [2-(4-nitrophenyl)-1-(S)-thiocarbamoylethyl]-carbamic acid tert-butyl ester, 2, (0.245 g, 0.753 mmol), 1-bromo-2-butanone (0.125 g, 0.828 mmol) in CH3CN (5 mL) is refluxed 3 hours. The reaction mixture is cooled to room temperature and diethyl ether is added to the solution and the precipitate which forms is removed by filtration. The solid is dried under vacuum to afford 0.242 g (90% yield) of the desired product. ESI+MS 278 (M+1).
Reaction SMILES: [CH2:1]([N:8]1[C:14](=O)[CH:13]2[N:16](C)[CH:10]([CH2:11][CH2:12]2)[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>CCOCC>[CH2:1]([N:8]1[CH2:14][CH:13]2[NH:16][CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN1C2CCC1C(=O)N(Cc1ccccc1)C2=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: c1ccc(CN2CC3CCC(C2)N3)cc1

Procedure:
A solution of 3-benzyl-2,4-dioxo-8-methyl-3,8-diazabicyclo (3.2.1)octane (2.05 g, 8.91 mmoles) in dry ether (100 mL) was treated gradually with lithium aluminum hydride (1.52 g, 4 mmoles), heated under reflux for one hour, and hydrolyzed successively with 50 mL of water-saturated ether and then 10 mL of water. This mixture was filtered on a celite pad. The filtrate was dried over magnesium sulfate and then evaporated to give the crude titled product which was used without any purification for further uses.
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([NH:7][C:8]([NH:10][S:11]([C:14]2[C:22]3[C:17](=[C:18]([O:23][CH2:24][C:25]([O:27]CC)=O)[CH:19]=[CH:20][CH:21]=3)[N:16]([CH3:30])[CH:15]=2)(=[O:13])=[O:12])=[O:9])=[N:4][CH:3]=1.[NH3:31].CO>>[Br:1][C:2]1[S:6][C:5]([NH:7][C:8]([NH:10][S:11]([C:14]2[C:22]3[C:17](=[C:18]([O:23][CH2:24][C:25]([NH2:31])=[O:27])[CH:19]=[CH:20][CH:21]=3)[N:16]([CH3:30])[CH:15]=2)(=[O:12])=[O:13])=[O:9])=[N:4][CH:3]=1
Reactant: N
Reactant: CCOC(=O)COc1cccc2c(S(=O)(=O)NC(=O)Nc3ncc(Br)s3)cn(C)c12
Solvent: CO
Product: Cn1cc(S(=O)(=O)NC(=O)Nc2ncc(Br)s2)c2cccc(OCC(N)=O)c21

Procedure:
A solution of ethyl {[3-({[(5-bromo-1,3-thiazol-2-yl)carbamoyl]amino}sulfonyl)-1-methyl-1H-indol-7-yl]oxy}acetate (0.050 g, 0.09 mmol) in 7N ammonia/methanol, (5 mL) was heated at 40° C. for 5 h. The reaction mixture was concentrated to dryness and dried under high vacuum to obtain the title compound (0.040 g) as a grey amorphous solid. MS (ISN): m/e 486.4, 488.3 (M−H)−
Reaction SMILES: CN(C)C=O.CS([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:18])[F:17])(=O)=O.[CH3:20][C:21]1[N:22]=[C:23]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[S:24][C:25]=1[C:26](O)=[O:27].C(=O)([O-])O.[Na+]>O>[CH3:20][C:21]1[N:22]=[C:23]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[S:24][C:25]=1[C:26]([O:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([CH3:19])=[C:16]([F:17])[F:18])=[O:27]
Reactant: Cc1nc(-c2ccccc2)sc1C(=O)O
Reactant: CC(CCCCOS(C)(=O)=O)=C(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(CCCCOC(=O)c1sc(-c2ccccc2)nc1C)=C(F)F
Temperature: 100 °C
Reaction time: 6 h
Yield: 73.7 %

Procedure:
To 10 ml of N,N-dimethylformamide were dissolved 0.50 g (2.2 mmol) of 6,6-difluoro-5-methyl-5-hexenyl methanesulfonate and 0.53 g (2.4 mmol) of 4-methyl-2-phenylthiazole-5-carboxylic acid, followed by the addition of 0.37 g (4.4 mmol) of sodium hydrogencarbonate and stirring at 100° C. for 6 hours. The reaction liquid was then poured in water and extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentration under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate:hexane=1:19) to obtain 0.57 g (yield: 74%) of 6,6-difluoro-5-methyl-5-hexenyl 4-methyl-2-phenylthiazole-5-carboxylate.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:24])[CH2:20][C:21]([OH:23])=O)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1.CN([P+](O[N:36]1N=N[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.NC1C=CC=CC=1>CN(C)C=O.CCOC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:19](=[O:24])[CH2:20][C:21]([NH:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[C:14]2=[CH:15][CH:16]=[CH:17][N:13]2[N:12]=[CH:11][N:10]=1
Reactant: O=C(O)CC(=O)Nc1ccc(Oc2ncnn3cccc23)c(F)c1
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: Nc1ccccc1
Solvent: CN(C)C=O
Product: O=C(CC(=O)Nc1ccc(Oc2ncnn3cccc23)c(F)c1)Nc1ccccc1

Procedure:
A solution of 3-(3-fluoro-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yloxy)phenylamino)-3-oxopropanoic acid (17 mg, 0.052 mmol), BOP reagent (34 mg, 0.077 mmol), 4-methylmorpholine (28 μL, 0.26 mmol), and aniline (4.7 μL, 0.052 mmol) in dimethylformamide (0.5 mL) was stirred at room temperature for 16 h. The reaction was diluted with EtOAc (4 mL) and washed with water, 10% aq LiCl solution, and brine (1×3 mL each). The organic solution was dried over anhydrous Na2SO4 and then concentrated in vacuo. Purification by flash chromatography on silica gel (SiO2, EtOAc/Hexane 7:3) gave the desired compound as a white solid. The product was lyophilized with acetonitrile/water to give the title compound (12 mg, 57%) as a white powder. 1H NMR (CDCl3) δ 9.23 (br s, 1H), 8.22 (br s, 1H), 7.90 (s, 1H), 7.72 (m, 1H), 7.46 (d, 1H, J=8.2 Hz), 7.20 (m, 7H), 6.95 (m, 1H), 6.78 (m, 1H), 3.47 (s, 2H); MS(ESI+) m/z 406.1 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1.[I-:13].[Na+].C(Cl)(=O)C>C(#N)C>[I:13][C:2]1[CH:7]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][N:3]=1
Reactant: Clc1cc(-c2cccs2)ccn1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(=O)Cl
Solvent: CC#N
Product: Ic1cc(-c2cccs2)ccn1
Temperature: 80 °C
Reaction time: 8 h
Yield: 89.5 %

Procedure:
A 20 mL microwave vial was charged with 2-chloro-4-thiophen-2-yl-pyridine (428 mg, 2.19 mmol), sodium iodide (3.28 g, 21.9 mmol) and acetonitrile (3.5 mL). Acetyl chloride (0.24 mL, 3.4 mmol) was added and the vial was flushed with Argon and closed. The reaction mixture was stirred at 80° C. overnight. The reaction mixture was cooled to room temperature and quenched with 10 mL saturated Na2CO3 solution then extracted with 50 mL dichloromethane. The organic layer was washed with 10 mL 10% Na2S2O3 solution. The aqueous layers were extracted twice with 50 mL dichloromethane. The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 24 g SiO2 with EtOAc/hexanes (gradient: 0-10% EtOAc). All fractions containing product were combined and concentrated to afford 563 mg (90%) of 2-iodo-4-thiophen-2-yl-pyridine as a light yellow solid.
Reaction SMILES: [BH4-].[Na+].C([C:7]1[S:11][C:10](C=S)=[CH:9][CH:8]=1)CCC.[CH3:14][OH:15]>[OH-].[Na+].C1COCC1>[OH:15][CH2:14][C:10]1[S:11][C:7]([S:11][CH2:10][CH2:9][CH2:8][CH3:7])=[CH:8][CH:9]=1
Reactant: CCCCc1ccc(C=S)s1
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCCCSc1ccc(CO)s1
Reaction time: 2 h

Procedure:
A solution of NaBH4 (5.3 g, 0.141 mol) in methanol (29.0 g) and sodium hydroxide (20%, 56.0 mL) was added dropwise to a solution of 45 (56.47 g, 0.282 mol) in THF (75 mL) at room temperature. The mixture was stirred for 2 hours, extracted with ethyl ether 3×150 mL), the combined extracts washed with brine and dried (MgSO4). After solvent removal, the crude product 46 was obtained as an oil (55.4 g, 97%); 1H NMR δ: 0.88 (t, 3 H, J=7.3 Hz, CH3), 1.39 (m, 2 H, CH3—CH2), 1.57 (m, 2 H, CH3—CH2—CH2),1.88 (s, 1 H OH), 2.76 (t, 2 H, J=7.3 Hz, CH2—S), 4.73 (s, 2 H, CH2—OH), 6.83 (d, 1 H, J=3.5 Hz, aromatic H), 6.94 (d, 1 H, J=3.5 Hz, aromatic H); λmax/nm (εmax/dm3 mol−1cm−1) 275.5 (3600); LRMS(EI+) calc. for C9H14OS2: 202.1, found 202.1. The product was used without further purification in the preparation of 47.
Reaction SMILES: [CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:5]1([NH:39][CH2:40][CH2:41][NH:42][C:43]1C=NC=CC=1)[CH2:4][CH2:3]2.Br[C:50]1[N:51](C)[CH:52]=[CH:53][N:54]=1.[Li+].[OH-].C(O)(C(F)(F)F)=O>CO.O>[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:5]1([NH:39][CH2:40][CH2:41][NH:42][C:43]1[N:51]([CH3:50])[CH:52]=[CH:53][N:54]=1)[CH2:4][CH2:3]2
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCNc3cccnc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: Cn1ccnc1Br
Agent: [Li+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Solvent: O
Product: C=C(C)[C@@H]1CC[C@]2(NCCNc3nccn3C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
The title compound was prepared following a similar procedure as described for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(2-(pyridin-3-ylamino)ethylamino)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, except 2-bromo-1-methyl-1H-imidazole (0.015 g, 8.88 μL, 0.091 mmol) was used in place of 3-bromopyridine. Also, addition of LiOH, water and methanol were unnecessary for this example, as the ester hydrolysis occurred spontaneously during the course of the amination reaction. The product was isolated after reverse phase preparative HPLC purification using Prep HPLC Method 8 as a beige solid (38.1 mg, 51.5% yield) bis TFA salt. LCMS: m/e 653.4 (M+H)+, 3.88 min (method 16). 1H NMR (500 MHz, 1:1 mixture of CDCl3 and MeOD, MeOD lock) δ ppm 7.91 (d, J=8.2 Hz, 2H), 7.19 (d, J=7.9 Hz, 2H), 6.86 (s, 1H), 6.83-6.79 (m, 1H), 5.28 (d, J=5.5 Hz, 1H), 4.84 (s, 1H), 4.73 (s, 1H), 4.71 (br. s., 1H), 3.98-3.82 (m, 2H), 3.58 (s, 3H), 3.25 (br. s., 1H), 2.89-2.78 (m, 1H), 2.18-2.07 (m, 3H), 2.05-1.92 (m, 3H), 1.90-1.79 (m, 1H), 1.72 (s, 4H), 1.69 (br. s., 1H), 1.62-1.54 (m, 3H), 1.53-1.47 (m, 3H), 1.46-1.34 (m, 5H), 1.28-1.20 (m, 2H), 1.18-1.12 (m, 1H), 1.11 (s, 3H), 1.09-1.03 (m, 4H), 1.01 (s, 3H), 0.93 (br. s., 3H), 0.93 (br. s., 3H).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])(=[O:13])=[O:12])=[CH:7][CH:6]=1.Cl[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:24]=1>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]([CH2:22][C:23]2[CH:32]=[CH:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)[CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])(=[O:12])=[O:13])=[CH:7][CH:6]=1
Reactant: CCOC(=O)CNS(=O)(=O)c1ccc(OC)cc1
Reactant: ClCc1ccc2ccccc2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CN(Cc1ccc2ccccc2n1)S(=O)(=O)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a suspension of sodium hydride (0.84 g, 35.0 mmol) in dimethylformamide (120.0 mL), is added ethyl 2-[[4-methoxybenzenesulfonyl]amino]acetate (3.19 g, 11.67 mmol) and 2- (chloromethyl)quinoline (2.62 g, 12.26 mmol), and the reaction is stirred for three days at room temperature. Then, additional NaH (0.46 g, 11.67 mmol) is added, and the reaction is heated to 50° C. for 5 hours. The reaction is cooled to 0° C., quenched with water, and extracted well with ether. The combined organic layers are washed with brine, dried (Na2SO4), and the solvent is removed to give ethyl 2-[[4-methoxybenzenesulfonyl]-(2-quinolinylmethyl)amino]acetate.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:26])[NH:4][C:5]2[C:10]([N:11]=1)=[C:9]([O:12][C:13]1[CH:18]=[C:17](Cl)[N:16]=[C:15]([NH:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[N:14]=1)[CH:8]=[CH:7][CH:6]=2.[CH2:27]([C@H:31]1[CH2:36][NH:35][CH2:34][CH2:33][N:32]1[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH:28]([CH3:30])[CH3:29]>>[NH2:1][C:2]1[C:3](=[O:26])[NH:4][C:5]2[C:10]([N:11]=1)=[C:9]([O:12][C:13]1[N:14]=[C:15]([NH:20][C@@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[N:16]=[C:17]([N:35]3[CH2:34][CH2:33][N:32]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[C@@H:31]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:36]3)[CH:18]=1)[CH:8]=[CH:7][CH:6]=2
Reactant: CC(C)C[C@H]1CNCCN1C(=O)OC(C)(C)C
Reactant: COC[C@H](C)Nc1nc(Cl)cc(Oc2cccc3[nH]c(=O)c(N)nc23)n1
Product: COC[C@H](C)Nc1nc(Oc2cccc3[nH]c(=O)c(N)nc23)cc(N2CCN(C(=O)OC(C)(C)C)[C@@H](CC(C)C)C2)n1

Procedure:
The reaction of (S)-3-amino-5-(6-chloro-2-(1-methoxypropan-2-ylamino)pyrimidin-4-yloxy)quinoxalin-2(1H)-one (74 mg, 0.2 mmol, Example 122(b)) with (S)-tert-butyl 2-isobutylpiperazine-1-carboxylate (48 mg, 0.2 mmol, CNH-Tech) under the conditions of Example 34 provided the title compound as an amorphous solid. MS (ESI, pos. ion) m/z: 583 (M+1).
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[N:16]=[CH:15][C:14]([C:17]([N:19]2[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[CH2:23][N:22]3[CH:30]=[CH:31][CH:32]=[C:21]3[CH2:20]2)=[O:18])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+]>[C:1]1([C:11]2[N:16]=[CH:15][C:14]([C:17]([N:19]3[C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=4[CH2:23][N:22]4[CH:30]=[CH:31][CH:32]=[C:21]4[CH2:20]3)=[O:18])=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(c1ccc(Cl)nc1)N1Cc2cccn2Cc2ccccc21
Reactant: OB(O)c1ccccc1
Agent: [Pd+]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=C(c1ccc(-c2ccccc2)nc1)N1Cc2cccn2Cc2ccccc21
Yield: 27.5 %

Procedure:
The title compound was prepared in the manner of Example 28 using phenylboronic acid (0.269 g), (6-chloro-pyridin-3-yl-[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Example 28, Step A (0.645 g) and palladium(I) acetate (0.01 7g), in a mixture of toluene (1 2 mL), 1 M aqueous sodium carbonate (4 mL) and ethanol (2 mL). The initially obtained foam (0.387 g) was purified by HPLC (Primesphere C18, 5×25 cm column eluting with 55% acetonitrile in water containing 0.1% formic acid) to yield the title product (0.200 g) as a yellow solid. Recrystallization of a sample from acetone/hexane yielded yellow needles, m.p. 171–174° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:13][C:12]([N+:21]([O-])=O)=[CH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1>C(O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[N:10]=[CH:11][C:12]([NH2:21])=[CH:13][C:14]=2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc(-c2ncc([N+](=O)[O-])cc2-c2ccccc2)c1
Agent: [Pd]
Solvent: CCO
Product: COc1cccc(-c2ncc(N)cc2-c2ccccc2)c1
Reaction time: 16 h
Yield: 68.9 %

Procedure:
A mixture of 2-(3-methoxyphenyl)-5-nitro-3-phenylpyridine (0.84 mmol, 0.257 g) and Pd/C 10% (0.08 mmol, 0.009 g) in ethanol (5 ml) was stirred for 16 hours under hydrogen atmosphere. The catalyst was filtered off and the solid thoughtfully washed with warm ethanol. The filtrate was evaporated and the crude was purified by chromatography over SiO2 eluting with DCM/methanol mixtures and affording 0.160 g (yield 69%) of the expected product.
Reaction SMILES: [OH:1][CH:2](CO)[CH2:3][CH2:4][CH2:5][C:6]1([CH2:35][CH2:36][CH2:37][CH:38]([OH:41])CO)[CH2:11][C:10](=[O:12])[C:9]2[CH:13]=[CH:14][C:15]([O:20][CH2:21][CH2:22][CH2:23][O:24][C:25]3[C:34]4[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=4[CH:28]=[CH:27][CH:26]=3)=[C:16]([CH2:17][CH2:18][CH3:19])[C:8]=2[O:7]1.I([O-])(=O)(=O)=O.[Na+]>C(O)(C)(C)C.O>[O:12]=[C:10]1[C:9]2[CH:13]=[CH:14][C:15]([O:20][CH2:21][CH2:22][CH2:23][O:24][C:25]3[C:34]4[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=4[CH:28]=[CH:27][CH:26]=3)=[C:16]([CH2:17][CH2:18][CH3:19])[C:8]=2[O:7][C:6]([CH2:35][CH2:36][CH2:37][CH:38]=[O:41])([CH2:5][CH2:4][CH2:3][CH:2]=[O:1])[CH2:11]1
Reactant: CCCc1c(OCCCOc2cccc3c2CCCC3)ccc2c1OC(CCCC(O)CO)(CCCC(O)CO)CC2=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Solvent: CC(C)(C)O
Product: CCCc1c(OCCCOc2cccc3c2CCCC3)ccc2c1OC(CCCC=O)(CCCC=O)CC2=O
Reaction time: 2 h
Yield: 60.9 %

Procedure:
To a solution of 200 mg (0.350 mmol) of the title product of Example 71 in 9.8 ml of t-butanol was added with stirring a solution of 300 mg (1.40 mmol) of sodium periodate in 2.2 ml of water. After two hours, the mixture was partitioned between diethyl ether and water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and the solvent removed under reduced pressure. The residue was chromatographed on a silica gel column, using ethyl acetate/hexane as eluent. Crystallization from diethyl ether/hexane gave 114 mg of the title compound, m.p. 72°-73° C.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[C:16]([Cl:21])[CH:15]=2)=[O:11])[CH2:6][CH2:5]1.[NH:22]1[CH:26]=[C:25]([CH2:27][CH2:28][C:29](O)=[O:30])[N:24]=[N:23]1>>[NH:24]1[C:25]([CH2:27][CH2:28][C:29]([NH:2][CH2:3][CH:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]3[CH:15]=[C:16]([Cl:21])[CH:17]=[C:18]([Cl:20])[CH:19]=3)=[O:11])[CH2:6][CH2:5]2)=[O:30])=[CH:26][N:22]=[N:23]1
Reactant: NCC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1
Reactant: O=C(O)CCc1c[nH]nn1
Agent: Cl
Product: O=C(CCc1cnn[nH]1)NCC1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1

Procedure:
The title compound was prepared from 3,5-dichlorobenzyl 4-(aminomethyl)piperidine-1-carboxylate hydrochloride (Example 41, step 2) and 3-(1H-1,2,3-triazol-4-yl)propanoic acid (step 1) analogously to Example 41 step 3;