Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OO.[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([F:15])[CH2:12][C@@H:11]1[C@@H:16]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[C@H:17]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:18]([N:20]1[C@@H](C(C)C)COC1=O)=[O:19])=[O:9])([CH3:6])([CH3:5])[CH3:4].[OH-].[Li+].C(N(C(C)C)CC)(C)C.C1(P([N:69]=[N+:70]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.C(OCC)(=O)C.ClCCl.CO>[C:3]([O:7][C:8]([N:10]1[CH2:14][C@H:13]([F:15])[CH2:12][C@@H:11]1[C@@H:16]([O:36][Si:37]([C:40]([CH3:43])([CH3:42])[CH3:41])([CH3:39])[CH3:38])[C@@H:17]([C:18]([N:20]=[N+:69]=[N-:70])=[O:19])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4]
Reactant: CC(C)[C@H]1COC(=O)N1C(=O)[C@@H](Cc1ccccc1)[C@H](O[Si](C)(C)C(C)(C)C)[C@H]1C[C@@H](F)CN1C(=O)OC(C)(C)C
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: OO
Agent: [Li+]
Agent: [OH-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)(C)OC(=O)N1C[C@H](F)C[C@@H]1[C@@H](O[Si](C)(C)C(C)(C)C)[C@H](Cc1ccccc1)C(=O)N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Add an aqueous solution of hydrogen peroxide (30% solution, 2.7 mL, 28.1 mmol) dropwise to a solution of 2-(R)-[2-(S)-benzyl-1-(S)-(tert-butyl-dimethylsilanyloxy)-3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxopropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester (2.779 g, 4.69 mmol) in THF (15 mL) at 0° C. Add 2 N lithium hydroxide (4.7 mL, 9.38 mmol) dropwise, stir 60 min and warm to room temperature. Add methanol (5 mL) and stir 18 h. Dilute with ethyl acetate and wash with 1 N HCl, saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate. Dissolve residue in dichloromethane (30 mL) and add diisopropylethylamine (1.2 mL, 7.03 mmol) followed by diphenylphosphoryl azide (1.1 mL, 5.16 mmol). Stir 1 h and add diisopropylethylamine (1.2 mL, 7.03 mmol) followed by diphenylphosphoryl azide (1.1 mL, 5.16 mmol). Stir 3.5 h, concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a residue (0.79 g, 32%).
Reaction SMILES: [CH2:1]([C@H:3]1[C@@H:7]([CH2:8][OH:9])[CH2:6][C:5](=[CH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:4]1)[CH3:2]>C(Cl)Cl.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CC=CCCC=C1.C1C=CN=CC=1.F[P-](F)(F)(F)(F)F.[Ir]>[CH2:1]([C@H:3]1[C@@H:7]([CH2:8][OH:9])[CH2:6][C@H:5]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:4]1)[CH3:2]
Reactant: CCOC(=O)C=C1C[C@@H](CC)[C@@H](CO)C1
Agent: [Ir]
Agent: C1=C\CC/C=C\CC/1
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Solvent: c1ccncc1
Solvent: C1=CCCC=CCC1
Solvent: ClCCl
Product: CCOC(=O)C[C@@H]1C[C@@H](CC)[C@@H](CO)C1
Reaction time: 24 h
Yield: 86.6 %

Procedure:
To a solution of ethyl 2-((3R,4S)-3-ethyl-4-(hydroxymethyl)cyclopentylidene)acetate (0.160 g, 0.754 mmol) in DCM (3 mL) was added Crabtree's catalyst (0.030 g, 0.038 mmol). The reaction mixture was sparged with hydrogen for about 5 min and an atmosphere of hydrogen was maintained via balloon. After about 24 h, the reaction mixture was concd in vacuo and purified by chromatography on silica gel eluting with EtOAc/heptane (30-80%) to provide ethyl 2-((1R,3R,4S)-3-ethyl-4-(hydroxymethyl)cyclopentyl)acetate (0.140 g, 87%) as an oil. 1H NMR (400 MHz, CDCl3) δ 4.12 (q, J=7.1 Hz, 2H), 3.71-3.64 (dd, J=10.5, 8.0 Hz, 1H), 3.47 (dd, J=10.5, 8.0 Hz, 1H), 2.55-2.41 (m, 1H), 2.32 (d, J=6.7 Hz, 2H), 2.02-1.89 (m, 1H), 1.88-1.76 (m, 1H), 1.70-1.60 (m, 1H), 1.48-1.33 (m, 4H), 1.26 (t, J=7.1 Hz, 3H), 1.22-1.07 (m, 1H), 0.90 (t, J=7.4 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([F:19])=[CH:17][CH:16]=[C:15]([O:20][CH2:21][CH2:22][O:23]C4CCCCO4)[C:14]=3[F:30])O)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:13]3[C:14]([F:30])=[C:15]([CH:16]=[CH:17][C:18]=3[F:19])[O:20][CH2:21][CH2:22][OH:23])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: OC(c1c(F)ccc(OCCOC2CCCCO2)c1F)c1c[nH]c2ncc(Br)cc12
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: OCCOc1ccc(F)c(Cc2c[nH]c3ncc(Br)cc23)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 35.2 %

Procedure:
To (5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-2,6-difluoro-3-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl-methanol (542, 0.22 g, 0.46 mmol) in acetonitrile (6.0 mL) were added trifluoroacetic acid (0.14 mL, 1.8 mmol) and triethylsilane (0.29 mL, 1.8 mmol). The reaction was stirred at room temperature overnight. The filtrate was concentrated and purified by silica gel column chromatography eluting with 35% ethyl acetate in hexane to give the compound as a white solid (P-1392, 62 mg, 35%). MS (M+H+)+=383.1, 385.1.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[CH3:12][C:13]1[N:18]=[C:17]([C:19]2[C:20](B(O)O)=[C:21]3[CH2:26][CH2:25][CH2:24][N:22]3[N:23]=2)[CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[CH3:12][C:13]1[N:18]=[C:17]([C:19]2[C:20]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[CH:8]=[N:7][CH:6]=[CH:5]4)=[C:21]3[CH2:26][CH2:25][CH2:24][N:22]3[N:23]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: Cc1cccc(-c2nn3c(c2B(O)O)CCC3)n1
Reactant: Ic1ccc2cnccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: Cc1cccc(-c2nn3c(c2-c2ccc4cnccc4c2)CCC3)n1
Temperature: 25 °C
Yield: 51.2 %

Procedure:
Dissolve 6-iodoisoquinoline (0.085 g, 0.333 mmol) and 2-(6-methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-3-boronic acid (Preparation 2; 0.077 g, 0.317 mmol) in dioxane (2.5 mL). Add 5M aqueous potassium carbonate (0.667 mL, 3.33 mmol) followed by triphenylphosphine (5.2 g, 0.020 mmol) and tris(dibenzylidineacetone)dipalladium (18 mg, 0.020 mmol). Reflux the mixture for 2 h and cool to room temperature. Load the reaction mixture on to a cartridge containing SCX resin (5 g) and wash the resin sequentially with 1 volume dichloromethane, 1 volume methanol, and 1 volume methanol containing 2N ammonia. Remove the organic solvents under reduced pressure. Chromatograph on 15 g silica gel eluting with 5% methanol in ethyl acetate to provide 0.053 g (48%) of the title compound as a tan solid.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][CH2:15][O:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([NH:27][C:28]([NH:30][C:31]3[N:35]([C:36]4[CH:41]=[CH:40][C:39]([CH3:42])=[CH:38][CH:37]=4)[N:34]=[C:33]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:32]=3)=[O:29])=[CH:19][CH:18]=2)[CH:11]=[CH:10][N:9]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[C:12]([CH2:14][CH2:15][O:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([NH:27][C:28]([NH:30][C:31]3[N:35]([C:36]4[CH:37]=[CH:38][C:39]([CH3:42])=[CH:40][CH:41]=4)[N:34]=[C:33]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:32]=3)=[O:29])=[CH:19][CH:18]=2)[CH:11]=[CH:10][N:9]=1
Reactant: Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(OCCc3ccnc(NC(=O)OC(C)(C)C)c3)c3ccccc23)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(OCCc3ccnc(N)c3)c3ccccc23)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 102 %

Procedure:
To a suspension of tert-butyl-4-(2-(4-(3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)ureido) naphthalen-1-yloxy)ethyl)pyridin-2-ylcarbamate (14) (1.35 g, 2.20 mmol) in DCM (10 mL) was added TFA (10 mL). After stirring at RT for 2 hr, the volatiles were evaporated and the residue was taken up in EtOAc (50 mL) and extracted with saturated aq NaHCO3 (50 mL). The layers were separated; the organic was washed with brine (50 mL), dried and evaporated to give 1-(4-(2-(2-aminopyridin-4-yl)ethoxy)naphthalen-1-yl)-3-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)urea (Intermediate D) as a pale pink solid (1.20 g, 100%): m/z 535 (M+H)+ (ES+).
Reaction SMILES: C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH2:16][C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])(=[O:15])=[O:14])=[CH:9][CH:8]=1.Br[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].[Cl-].[NH4+]>CCCCCC.C(OCC)(=O)C.C(COC)OC.CCCCCC>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([S:13]([CH:16]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])(=[O:15])=[O:14])=[CH:9][CH:8]=1
Reactant: O=S(=O)(Cc1cc(F)ccc1F)c1ccc(Cl)cc1
Reactant: CC(C)(C)OC(=O)CBr
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: COCCOC
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CC(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Under an argon atmosphere and at −78° C., n-butyl lithium (a 1.57M hexane solution, 7.01 ml) was added dropwise to a dimethoxyethane solution (50 ml) of the 2-[(4-chlorophenyl)sulfonylmethyl]-1,4-difluorobenzene (3.03 g, 10.0 mmol) obtained in Example 5. The temperature of the reaction mixture was raised to room temperature. Then, the reaction mixture was cooled to −78° C. After the addition of t-butyl bromoacetate (1.48 ml, 10.0 mmol), the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was added with a saturated aqueous ammonium chloride solution, followed by extraction with diethyl ether. The extracts were combined, washed successively with water and brine, dried over MgSO4, and then distilled to remove the solvent. The residue thus obtained was subjected to chromatography on a short silica gel column (hexane-ethyl acetate 3:1). The solid thus obtained was recrystallized from hexane, whereby the title compound (3.30 g, 79%) was obtained as a colorless solid.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][NH2:9])[CH2:3][CH2:2]1.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([S:18](Cl)(=[O:20])=[O:19])[CH:15]=[CH:16][CH:17]=1>C(Cl)Cl.N1C=CC=CC=1>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([S:18]([NH:9][CH2:8][CH2:7][N:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)(=[O:20])=[O:19])[CH:15]=[CH:16][CH:17]=1
Reactant: NCCN1CCOCC1
Reactant: COc1cccc(S(=O)(=O)Cl)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COc1cccc(S(=O)(=O)NCCN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.8 %

Procedure:
2-Morpholinoethylamine (1.75 mL, 13.3 mmol) was added over 10 min to a solution of 3-(methyloxy)benzenesulfonyl chloride (2.5 g, 12.1 mmol) in CH2Cl2 (10 mL) and pyridine (4 mL) and the resulting solution was stirred at rt for 1 h. The mixture was concentrated, dissolved in EtOAc and the organic phase was washed with H2O and brine, dried (MgSO4), filtered and the filtrate was concentrated to give an orange oil (3.3 g, 92%) which was used directly in the next step. MS (ES+) m/e 301 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](OC)=[O:7])=[C:4]([CH3:12])[CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CCOCC>[Br:1][C:2]1[CH:11]=[CH:10][C:5]([CH2:6][OH:7])=[C:4]([CH3:12])[CH:3]=1
Reactant: COC(=O)c1ccc(Br)cc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: Cc1cc(Br)ccc1CO
Reaction time: 3 h

Procedure:
A solution of methyl 4-bromo-2-methyl-benzoate (1.05 g, 4.58 mmols) in 10 mL of Et2O was cooled to 0° C. and treated with LiAlH4 (177.0 mg, 4.58 mmols), stirred for 3 hours, and then carefully quenched with H2O. The mixture was extracted with Et2O and the combined organic layers were washed with H2O and saturated aqueous NaCl, dried (MgSO4), and concentrated under reduced pressure. The title compound, 830.0 mg (90%), was isolated by column chromatography (10-30% EtOAc-hexanes) as a colorless oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)(=[O:10])=[O:9])=[C:4]([F:16])[CH:3]=1.[C:17]([C:19]1[N:23]([CH3:24])[C:22](B(O)O)=[CH:21][CH:20]=1)#[N:18].[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:17]([C:19]1[N:23]([CH3:24])[C:22]([C:2]2[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH:12]3[CH2:15][CH2:14][CH2:13]3)(=[O:10])=[O:9])=[C:4]([F:16])[CH:3]=2)=[CH:21][CH:20]=1)#[N:18]
Reactant: O=S(=O)(NC1CCC1)c1ccc(Br)cc1F
Reactant: Cn1c(C#N)ccc1B(O)O
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: Cn1c(C#N)ccc1-c1ccc(S(=O)(=O)NC2CCC2)c(F)c1
Reaction time: 16 h
Yield: 12.7 %

Procedure:
According to general procedure B, 4-bromo-N-cyclobutyl-2-fluorobenzenesulfonamide (185 mg, 0.59 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (106 mg, 0.70 mmol), potassium fluoride (113 mg, 1.95 mmol), and tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.01 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.4 mL) was added. Tri-t-butylphosphine (89 μL, 0.02 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-cyclobutyl-2-fluorobenzenesulfonamide (25 mg, 13%) was provided after purification. MS (ESI) m/z 333. HPLC purity 99.6% at 210-370 nm, 9.3 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:60]=[CH:61][CH:62]=1)[CH2:45][N:46]1[CH2:50][CH2:49][N:48]([C@@H:51]([C:55]([CH3:58])([CH3:57])[CH3:56])[C:52](O)=[O:53])[C:47]1=[O:59].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[OH:32][C@H:3]([C@@H:2]([NH:1][C:52](=[O:53])[C@@H:51]([N:48]1[CH2:49][CH2:50][N:46]([CH2:45][C:44]2[CH:60]=[CH:61][CH:62]=[C:42]([O:41][CH3:40])[CH:43]=2)[C:47]1=[O:59])[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1
Reactant: COC(=O)N[C@H](C(=O)N[C@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@@H](N)Cc1ccccc1)C(C)(C)C
Reactant: COc1cccc(CN2CCN([C@H](C(=O)O)C(C)(C)C)C2=O)c1
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COC(=O)N[C@H](C(=O)N[C@H](Cc1ccc(-c2ccccn2)cc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N1CCN(Cc2cccc(OC)c2)C1=O)C(C)(C)C)C(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 56.7 %

Procedure:
A solution containing the product from Example 1H (0.020 g, 0.038 mmol) in THF (0.4 mL) was treated with the product from Example 71A (0.018 g, 0.056 mmol), DEPBT (0.017 g, 0.057 mmol), and N,N-diisopropylethylamine (0.033 mL, 0.189 mmol), stirred at 25° C. for 2 hours, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was purified by reversed phase chromatography on a C18 column eluting with 5-100% acetonitrile in water (0.1% TFA). The product was partitioned between ethyl acetate and saturated NaHCO3 solution. The organic phase was washed brine, dried over MgSO4, filtered and concentrated to give the title compound (0.018 g, 54% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.87 (s, 9 H), 1.25 (m, 1 H), 1.39 (m, 1 H), 1.54 (m, 1 H), 2.42 (m, 1 H), 2.64 (m, 3 H), 2.89 (m, 2 H), 3.21 (m, 1 H), 3.54 (m, 4 H), 3.72 (s, 3 H), 3.84 (d, J=9.56 Hz, 1 H), 3.96 (m, 1 H), 4.04 (s, 1 H), 4.18 (m, 1 H), 4.27 (s, 2 H), 4.44 (d, J=6.99 Hz, 1 H), 6.85 (m, 4 H), 7.06 (m, 5 H), 7.29 (m, 4 H), 7.54 (d, J=9.56 Hz, 1 H), 7.89 (m, 5 H), 8.65 (d, J=4.41 Hz, 1 H).
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[C:17]([Cl:22])[CH:16]=1)=[CH:10][CH:9]=2)=[O:5])C.[CH:23]([O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)([CH3:25])[CH3:24]>>[Cl:22][C:17]1[CH:16]=[C:15]([C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[N:7]([C:30]2[CH:31]=[CH:32][C:27]([O:26][CH:23]([CH3:25])[CH3:24])=[CH:28][CH:29]=2)[C:6]([C:4]([OH:3])=[O:5])=[CH:14]3)[CH:20]=[C:19]([Cl:21])[CH:18]=1
Reactant: CCOC(=O)c1cc2cc(-c3cc(Cl)cc(Cl)c3)ccc2[nH]1
Reactant: CC(C)Oc1ccc(B(O)O)cc1
Product: CC(C)Oc1ccc(-n2c(C(=O)O)cc3cc(-c4cc(Cl)cc(Cl)c4)ccc32)cc1

Procedure:
The title compound was prepared in accordance with Example 8(c) from 5-(3,5-dichlorophenyl)-1H-indole-2-carboxylic acid ethyl ester (see step (a) above) and 4-isopropoxyphenylboronic acid, followed by ester hydrolysis in accordance with the procedure described in Example 35, Method 3, step (b).
Reaction SMILES: C[N:2](C(C(C1C=CC=CC=1)(C1C=CC=CC=1)CCN1CCC(O)(C2C=CC(Cl)=CC=2)CC1)=O)C.Cl.C1OC1.[C:39]([O:44][CH2:45][CH2:46]O)(=[O:43])C(C)=C.[C:48]([O:53][CH3:54])(=[O:52])[C:49]([CH3:51])=[CH2:50].C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>>[NH2:2][C:39]([O:44][CH2:45][CH3:46])=[O:43].[C:48]([O:53][CH3:54])(=[O:52])[C:49]([CH3:51])=[CH2:50]
Reactant: CN(C)C(=O)C(CCN1CCC(O)(c2ccc(Cl)cc2)CC1)(c1ccccc1)c1ccccc1
Reactant: C=C(C)C(=O)OCCO
Agent: C=C(C)C(=O)OC
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: C1CO1
Product: CCOC(N)=O

Procedure:
A polyisocyanate having an average functionality of 2.6 (Suprasec (RTM) DND, ex ICI: 354 grams), a propoxylated glycerol end-capped with ethylene oxide and having a molecular weight of about 6000 (Daltocel (RTM) F2805, ex ICI; 240 grams), 2-hydroxyethyl methacrylate (338.5 grams) and methyl methacrylate (900.3 grams) were mixed and stirred under nitrogen. Dibutyl tin dilaurate (7 grams) was added with stirring and the reaction temperature rose to 70° C. After 2 hours the isocyanate concentration had fallen to below 2000 ppm. A mixture of an unsaturated urethane and methyl methacrylate, in approximately 1:1 weight ratio, was obtained as a brown liquid, (hereinafter referred to for convenience as Resin A).
Reaction SMILES: [CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][N:5]([CH3:25])[C:6]1[S:7][C:8]2[CH:14]=[C:13]([NH:15][C:16]([C:18]3[CH:23]=[N:22][C:21](Cl)=[CH:20][N:19]=3)=[O:17])[CH:12]=[CH:11][C:9]=2[N:10]=1.[Cl:27][C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:29]=1B(O)O>>[CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][N:5]([CH3:25])[C:6]1[S:7][C:8]2[CH:14]=[C:13]([NH:15][C:16]([C:18]3[CH:23]=[N:22][C:21]([C:29]4[CH:30]=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:28]=4[Cl:27])=[CH:20][N:19]=3)=[O:17])[CH:12]=[CH:11][C:9]=2[N:10]=1
Reactant: COc1ccc(B(O)O)c(Cl)c1
Reactant: CN(C)CCN(C)c1nc2ccc(NC(=O)c3cnc(Cl)cn3)cc2s1
Product: COc1ccc(-c2cnc(C(=O)Nc3ccc4nc(N(C)CCN(C)C)sc4c3)cn2)c(Cl)c1

Procedure:
The title compound is prepared by following a procedure analogous to Example 113, Step 1, using 5-chloro-pyrazine-2-carboxylic acid {2-[(2-dimethylamino-ethyl)-methyl-amino]-benzothiazol-6-yl}-amide (0.10 g, 0.26 mmol) and 2-chloro-4-methoxy-phenyl boronic acid (0.057 g, 0.31 mmol) to afford 0.062 g (48%). LC/MS, Retention time=4.89 nm in; (m/z): calcd for C24H25ClN6O2S: 497.0; found: 499.0.
Reaction SMILES: [CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11](Cl)=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.CN1C(=O)CCC1.C(N(CC)CC)C>ClCCl>[CH2:1]([C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1nnc(Cc2ccccc2)c2ccccc12
Reactant: C1CNCCN1
Solvent: CCN(CC)CC
Solvent: CN1CCCC1=O
Solvent: ClCCl
Product: c1ccc(Cc2nnc(N3CCNCC3)c3ccccc23)cc1
Yield: 58.6 %

Procedure:
1-Benzyl-4-chlorophthalazine (1.06 g, 4.18 mmol) and piperazine (1.82 g, 20.9 mmol) are added into a microwave vial, followed by NMP (5 ml) and triethylamine (6.62 ml, 12.5 mmol). The vial is sealed and irradiated in the microwave at 180° C. (high absorption setting) for 30 minutes. Dichloromethane (10 mL) is added to form a precipitate, which is washed with additional dichloromethane and dried under reduced pressure to afford the product as a white powder (745 mg, 58% yield).
Reaction SMILES: [C:1]1([CH:7]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9](=[O:14])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15](=O)([O:18]C)[O:16][CH3:17].[H-].[Na+]>CO>[O:14]=[C:9]1[CH2:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:13][CH2:12][CH2:11][CH:10]1[C:15]([O:16][CH3:17])=[O:18]
Reactant: COC(=O)OC
Reactant: O=C1CCCCC(c2ccccc2)C1
Agent: [H-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)C1CCCC(c2ccccc2)CC1=O
Temperature: 25 °C

Procedure:
A mixture of 3-phenylcycloheptanone (1.88 g, 9.99 mmol) and 5 drops of methanol in dimethyl carbonate (1.68 mL, 20.0 mmol) was treated with sodium hydride (60% dispersion, 800 mg, 20.0 mmol). The reaction was then refluxed for 2 hours before being cooled back to room temperature. The reaction was quenched with 2 M hydrochloric acid and extracted with ether, then chromatographed on silica gel (15% ethyl acetate/hexane, eluant) to afford the title compound as a colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 7.26 (m, 5H), 3.81 (dd, J=11.70, 3.77 Hz, 1H), 3.63 (s, 3H), 3.17 (m, 2H), 1.86 (m, 6H); MS (DCI+) m/z 247 (M+H)+, 264 (M+NH4)+.
Reaction SMILES: [Si]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:21][C:17]1[CH:16]=[C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@@H:10]2[CH2:9][OH:8])[CH:20]=[CH:19][CH:18]=1
Reactant: Cc1cccc(N2CCC[C@@H]2CO[Si](C)(C)C(C)(C)C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1cccc(N2CCC[C@@H]2CO)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 80.6 %

Procedure:
A solution of D4 (7.20 g, 0.024 mol) in THF (50 ml) was treated with tetrabutylammonium fluoride (1M solution in THF, 2 eq., 96 ml) and then stirred at ambient temperature for 18 h. Solvent was removed under reduced pressure and residue chromatographed on silica gel eluting with EtOAc in hexane (gradient elution, maximum 50%) to afford the product as an oil (3.70 g, 81%).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[CH:19]=[CH:18][CH:17]=[C:13]([C:14](O)=[O:15])[C:12]=3[C:20]([OH:22])=O)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.Br.[NH2:24][C@@:25]1([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32]>N1C=CC=CC=1>[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][C:11]3[CH:19]=[CH:18][CH:17]=[C:13]4[C:12]=3[C:20](=[O:22])[N:24]([C@@:25]3([CH3:33])[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]3=[O:32])[C:14]4=[O:15])=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: C[C@]1(N)CCC(=O)NC1=O
Reactant: O=C(O)c1cccc(Nc2ccc3c(c2)CCC3)c1C(=O)O
Agent: Br
Solvent: c1ccncc1
Product: C[C@]1(N2C(=O)c3cccc(Nc4ccc5c(c4)CCC5)c3C2=O)CCC(=O)NC1=O
Yield: 45 %

Procedure:
A mixture of 3-(indan-5-ylamino)-phthalic acid (0.62 g, 3.1 mmol) and (3S)-3-amino-3-methyl-piperidine-2,6-dione hydrobromide (0.50 g, 2.1 mmol) in pyridine (10 mL) was heated to reflux for 17 hours. The mixture was cooled and evaporated under vacuum. The residue was dissolved in ethyl acetate (100 mL), washed with dilute aqueous HCl (2×100 mL) and water (2×100 mL), and evaporated. The residue was purified by ISCO silica gel flash chromatography using a hexanes-ethyl acetate gradient, eluting 0.37 g of the product, an orange solid, at 70:30 hexanes-ethyl acetate, in 45% yield: mp 200-202° C.; HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 65/35 (CH3CN/0.1% H3PO4): tR=5.40 (99.54%); 1H NMR (DMSO-d6) δ 1.91 (s, 3H), 2.00-2.08 (m, 3H), 2.54-2.75 (m, 3H), 2.82-2.88 (m, 4H), 7.04-7.31 (m, 5H), 7.55 (t, J=7.8 Hz, 1H), 8.30 (s, 1H), 11.00 (s, 1H); 13C NMR (DMSO-d6) δ 21.0, 25.2, 28.6, 29.2, 31.8, 32.4, 58.5, 110.9, 112.4, 118.7, 120.7, 124.9, 132.2, 136.0, 137.2, 139.9, 143.4, 145.1, 167.8, 169.4, 172.2, 172.3; Anal. calcd for C23H21N3O4: C, 68.47; H, 5.25; N, 10.42. Found: C, 68.25; H, 5.12; N, 10.30.