Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10](I)[N:11]=1)[CH2:7][CH2:6][O:5]2.N([Si](C)(C)C)[Si](C)(C)C.C[N:27]([CH:29]=[O:30])C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:29]([NH2:27])=[O:30])[N:11]=1)[CH2:7][CH2:6][O:5]2
Reactant: CN(C)C=O
Reactant: Clc1cc2c(cn1)-c1nc(I)cn1CCO2
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Product: NC(=O)c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Temperature: 70 °C
Reaction time: 4 h
Yield: 97 %

Procedure:
To a solution of 12-chloro-4-iodo-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (10.0 g, 28.7 mmol) in dry DMF (300 mL) was added Pd(PPh3)2Cl2 (1.00 g, 1.44 mmol) and (Me3Si)2NH (86.1 mmol, 14.0 g). The mixture was stirred at 70° C. for 4 h under carbon monoxide atmosphere. After removal of the solvent, the residue was treated with ice-water. The solid was collected by filtration, dissolved in ethyl acetate (400 ml), dried over anhydrous Na2SO4, and concentrated to give 12-chloro-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene-4-carboxamide (7.20 g, 97% yield), which was used in the next step without further purification. LCMS (ESI) m/z: 265.1 [M+H+]
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH2:13][CH:14]([OH:17])CO)=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.O.I([O-])(=O)(=O)=O.[Na+].[Cl-].[Na+]>O1CCCC1.CO>[CH3:1][O:2][C:3]1[C:4]([CH2:13][CH:14]=[O:17])=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2
Reactant: COc1ccc2ncccc2c1CC(O)CO
Agent: [Cl-]
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc2ncccc2c1CC=O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 103 %

Procedure:
0.81 g of 3-(6-methoxyquinolin-5-yl)propane-1,2-diol was dissolved in 24 ml of tetrahydrofuran and 8 ml of methanol. Then, 12 ml of water containing 1.49 g of sodium metaperiodate was added to the reaction solution while cooling on ice, and the obtained mixture was then stirred at room temperature for 45 minutes. Thereafter, a saturated sodium chloride aqueous solution was added to the reaction solution, followed by extraction with methylene chloride. The extract was dried over magnesium sulfate and then concentrated under a reduced pressure, so as to obtain 0.72 g of (6-methoxyquinolin-5-yl)acetaldehyde. This compound was directly used in the following reaction without further purification.
Reaction SMILES: Br[C:2]1[C:3](=[O:18])[N:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[CH:5]=[CH:6][CH:7]=1.C[O:20][B:21](OC)[O:22]C.[Li]CCCC>C1COCC1>[CH3:17][N:13]1[C:14]2[C:10](=[CH:9][C:8]([N:4]3[CH:5]=[CH:6][CH:7]=[C:2]([B:21]([OH:22])[OH:20])[C:3]3=[O:18])=[CH:16][CH:15]=2)[CH:11]=[N:12]1
Reactant: COB(OC)OC
Reactant: Cn1ncc2cc(-n3cccc(Br)c3=O)ccc21
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cn1ncc2cc(-n3cccc(B(O)O)c3=O)ccc21

Procedure:
To a stirred and cooled (−78° C.) solution of 3-bromo-1-(1-methyl-1H-indazol-5-yl)pyridin-2(1H)-one (87 mg, 0.287 mmol) and trimethylborate (137 μL, 1.234 mmol) in anhydrous THF (5.0 mL) was added n-BuLi (2.5 M in hexane, 0.71 mL) for 10 min. Quenched the reaction by water and then purified by reverse phase HPLC, eluting by 0-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+ (m/z): [M+H]+ calcd for C13H13BN3O3: 270.1; found: 270.2.
Reaction SMILES: O[CH2:2][CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6]([C:15]2[C:16](=[O:31])[NH:17][C:18](=[O:30])[C:19]=2[C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:28]=2[N:27]([CH3:29])[CH:26]=[CH:25]3)=[CH:5]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Br)(Br)(Br)[Br:52]>C(Cl)Cl.C1COCC1.CCOC(C)=O>[Br:52][CH2:2][CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6]([C:15]2[C:16](=[O:31])[NH:17][C:18](=[O:30])[C:19]=2[C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:28]=2[N:27]([CH3:29])[CH:26]=[CH:25]3)=[CH:5]1
Reactant: BrC(Br)(Br)Br
Reactant: COc1ccc2c(C3=C(c4cccc5ccn(C)c45)C(=O)NC3=O)cn(CCO)c2c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: C1CCOC1
Product: COc1ccc2c(C3=C(c4cccc5ccn(C)c45)C(=O)NC3=O)cn(CCBr)c2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
To a solution of 3-[1-(2-hydroxyethyl)-6-methoxy-1H-indol-3-yl]-4-(1-methyl-1H-indol-7-yl)pyrrole-2,5-dione (7.3 g, 17.7 mmol) in a mixture of CH2Cl2 (360 mL) and THF (240 mL) was added PPh3 (4.6 g, 17.7 mmol) and CBr4 (5.8 g, 17.7 mmol). The reaction mixture was stirred at room temperature and under nitrogen for 1 h. Another equivalent of PPh3 (4.6 g, 17.7 mmol) was added followed by an equivalent of CBr4 (5.8 g, 17.7 mmol). This operation was repeated one more time after 1 h. The reaction was monitored by TLC and was completed after 1 h. The reaction mixture was diluted with EtOAc (300 mL) and washed with saturated aqueous NaHCO3 (500 mL), and brine (500 mL). The organic solution was dried (MgSO4), filtered and concentrated. Flash chromatography (SiO2, 50% EtOAc/hexanes) gave the title compound (6.5 g, 77%) as a red solid. 1H NMR (300 MHz, DMSO-d6) 11.08 (s, 1H), 7.95 (s, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.23 (d, J=3.1 Hz, 1H), 7.03–6.96 (m, 3H), 6.88 (d, J=6.2 Hz, 1H), 6.47 (d, J=3.1 Hz, 1H), 6.13 (s, 1H), 4.60 (t, J=6.0 Hz, 2H), 3.81 (t, J=6.0 Hz, 2H), 3.69 (s, 3H), 3.65 (s, 3H).
Reaction SMILES: Cl[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[CH3:13][NH2:14]>>[CH3:13][NH:14][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: O=Cc1ccc(Cl)c([N+](=O)[O-])c1
Reactant: CN
Product: CNc1ccc(C=O)cc1[N+](=O)[O-]

Procedure:
4-Chloro-3-nitro-benzaldehyde is reacted with methylamine to yield 4-(methylamino)-3-nitrobenzaldehyde (8) which is then reduced by NaBH4 to N-methyl-4-hydroxymethyl-2-nitroaniline (9). Reaction of SOCl2 with 8 will give N-methyl-4-chloromethyl-2-nitroaniline (10). Structures of 8, 9 and 10 may be characterized by 1H NMR and elemental analysis. 10 is used as an electrophile to react with sodium CD alkoxide (11) to yield 2-O-(4-methylamino-3-nitro) benzyl-β-CD (12). The addition of 10 to 11 is a novel method for mono-functionalizing the 2-position of CD's (Rong, P., and D'Souza, V. T., Tetrahedron Lett., 31:4275 (1990)). 12 is hydrogenated by agents such as H2 /Pd, H2 /Pt, H2 /Ni, Sn/HCl, Fe/HCl and Zn/HCl, and then condensed with alloxan monohydrate to yield 2-flavo-CD (13). Compounds 11 and 12 can be characterized by 1H and 13C NRM. 2-Flavo-α-CD, β-CD and γ-CD may be synthesized by the same method. ##STR12##
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]2([CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[O:17][C:16](=[O:18])[CH2:15][C:14](=[O:19])[CH2:13]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].P([O-])(O)(O)=O.[Na+].C(NC1C=CC(S([N:44]=[N+:45]=[N-])(=O)=O)=CC=1)(=O)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][C:12]2([CH:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)[O:17][C:16](=[O:18])[C:15](=[N+:44]=[N-:45])[C:14](=[O:19])[CH2:13]2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: COc1ccc(CCC2(C3CCCC3)CC(=O)CC(=O)O2)cc1Cl
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(CCC2(C3CCCC3)CC(=O)C(=[N+]=[N-])C(=O)O2)cc1Cl
Reaction time: 4 h
Yield: 99 %

Procedure:
To a solution of 6-[2-(3-chloro-4-methoxy-phenyl)-ethyl]-6-cyclopentyl-dihydro-pyran-2,4-dione (0.500 g, 1.44 mmol) from Example B(87), and sodium dihydrogen phosphate (0.26 g, 2.16 mmol) in DMF (6 mL) was added 4-acetamidobenzenesulfonyl azide (0.52 g, 2.16 mmol). The reaction was stirred for 4 hours, and then concentrated by rotary evaporation. The crude material was purified by flash chromatography to yield the desired compound (0.537 g, 100% yield).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:22]([C:23](=O)/[CH:24]=[CH:25]/N(C)C)=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([NH:16][CH:17]4[CH2:21][CH2:20][CH2:19][CH2:18]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.S(O)(O)(=O)=O.[NH2:35][C:36]([NH2:38])=[NH:37]>>[NH2:37][C:36]1[N:38]=[C:23]([C:22]2[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=3)=[N:9][N:10]3[C:15]([NH:16][CH:17]4[CH2:18][CH2:19][CH2:20][CH2:21]4)=[CH:14][CH:13]=[CH:12][C:11]=23)[CH:24]=[CH:25][N:35]=1
Reactant: CN(C)/C=C/C(=O)c1c(-c2cccc(Br)c2)nn2c(NC3CCCC3)cccc12
Reactant: N=C(N)N
Agent: O=S(=O)(O)O
Product: Nc1nccc(-c2c(-c3cccc(Br)c3)nn3c(NC4CCCC4)cccc23)n1
Yield: 76.9 %

Procedure:
In a similar manner as described in Example 1 from (2E)-1-[2-(3-bromophenyl)-7-(cyclopentylamino)pyrazolo[1,5-a]pyridin-3-yl]-3-(dimethylamino)-2-propen-1-one (500 mg, 1.1 mmol) and guanidine sulfate (358 mg, 1.65 mmol), N-[3-(2-amino-4-pyrimidinyl)-2-(3-bromophenyl)pyrazolo[1,5-a]pyridin-7-yl]-N-cyclopentylamine (380 mg, 77%) was obtained as a yellow solid. 1H NMR (CDCl3): δ 8.01 (d, 1H), 7.84 (s, 1H), 7.64 (d, 1H), 7.54–7.49 (m, 2H), 7.30–7.22 (m, 2H), 6.36 (d, 1H), 6.01 (d, 1H), 5.97 (d, 1H), 4.95 (broad s, 2H), 3.97 (m, 1H), 2.12 (m, 2H), 1.79–1.57 (m, 6H); MS m/z 448 (M+1); Anal. Calcd. for C22H21N6Br: C, 58.80; H, 4.71; N,18.70. Found: C, 58.61; H, 4.75; N, 18.58.
Reaction SMILES: [NH2:1][C:2]1[C:11]([NH2:12])=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Cl.N[C:15](OCC)=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>CCO>[CH2:20]([O:19][C:17](=[O:18])[CH2:16][C:15]1[NH:12][C:11]2[CH:10]=[CH:9][CH:8]=[C:3]([C:4]([O:6][CH3:7])=[O:5])[C:2]=2[N:1]=1)[CH3:21]
Reactant: COC(=O)c1cccc(N)c1N
Reactant: CCOC(=O)C=C(N)OCC
Agent: Cl
Solvent: CCO
Product: CCOC(=O)Cc1nc2c(C(=O)OC)cccc2[nH]1
Yield: 106.2 %

Procedure:
A solution of methyl 2,3-diaminobenzoate (680 mg) and ethyl 3-amino-3-ethoxyacrylate hydrochloride (880 mg) in EtOH (12 mL) was stirred at 60° C. for 2 hours. EtOH was removed under reduced pressure, and the residue was purified on column chromatography to obtain the titled compound (1.14 g) as a pale yellow solid.
Reaction SMILES: [OH:1][B:2]1[C:6]2[CH:7]=[C:8]([NH:11][S:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21]C(=O)C(F)(F)F)=[CH:17][C:16]=3[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])(=[O:14])=[O:13])[CH:9]=[CH:10][C:5]=2[CH2:4][O:3]1.N>>[NH2:21][C:18]1[CH:19]=[CH:20][C:15]([S:12](=[O:13])(=[O:14])[NH:11][C:8]2[CH:9]=[CH:10][C:5]3[CH2:4][O:3][B:2]([OH:1])[C:6]=3[CH:7]=2)=[C:16]([CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH:17]=1
Reactant: CCOC(=O)Cc1cc(NC(=O)C(F)(F)F)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Agent: N
Product: CCOC(=O)Cc1cc(N)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Yield: 54 %

Procedure:
Ethyl 2-(2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)-5-(2,2,2-trifluoroacetamido)phenyl)acetate (0.45 g, 0.92 mmol) and NH3 (7M in MeOH, 5 mL) was heated to 80° C. for 2 hrs. The reaction was monitored by LC/MS. Purification: The solvent was removed in vacuo and the product was recrystallized from EtOAc/MeOH to give 194 mg of the title compound as a white solid (yield: 54%). 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.88 (s, 1H), 9.17 (bs, 1H), 7.48 (d, J=9.2 Hz, 1H), 7.41 (d, J=0.9 Hz, 1H), 7.21 (d, J=8 Hz, 1H), 7.10 (dd, J=8.4, 2 Hz, 1H), 6.41 (m, 2H), 5.93 (s, 2H), 4.86 (s, 2H), 4.05 (q, J=7.6 Hz, 2H), 3.87 (s, 2H), 1.17 (t, J=7.2 Hz, 3H); MS (ESI) m/z=389.1 (M−H, negative).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:26][CH2:27][CH2:28]O)[CH2:9][C@@H:10]([NH:12][S:13]([C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[CH:22]=[N:21][CH:20]=[CH:19]2)(=[O:15])=[O:14])[CH3:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[CH2:32]([C@@H]1CNCCCN1S(C1C=C2C(=CC=1)C=NC=C2)(=O)=O)C.Cl.Cl.CN[C@H]1CCN(S(C2C=C3C(=CC=2)C=NC=C3)(=O)=O)C1>>[C:1]([O:5][C:6]([N:8]1[CH2:26][CH2:27][CH2:28][N:12]([S:13]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[CH:22]=[N:21][CH:20]=[CH:19]3)(=[O:15])=[O:14])[C@H:10]([CH2:11][CH3:32])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: C[C@@H](CN(CCCO)C(=O)OC(C)(C)C)NS(=O)(=O)c1ccc2cnccc2c1
Reactant: CC[C@@H]1CNCCCN1S(=O)(=O)c1ccc2cnccc2c1
Agent: CN[C@H]1CCN(S(=O)(=O)c2ccc3cnccc3c2)C1
Agent: Cl
Product: CC[C@@H]1CN(C(=O)OC(C)(C)C)CCCN1S(=O)(=O)c1ccc2cnccc2c1

Procedure:
The compound of interest was synthesized according to the production method of Step 1 of Example 12 using Reference Compound 2 and using Reference Compound 19 instead of Reference Compound 10.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[NH:13][C:14](=[O:34])[CH:15]([C:17]1[N:18]=[N:19][N:20]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[N:21]=1)Br)([CH3:3])[CH3:2].[N-:35]=[N+]=[N-].[Na+].[BH4-].[Na+]>C(O)C.C(OCC)(=O)C>[NH2:35][CH:15]([C:17]1[N:18]=[N:19][N:20]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[N:21]=1)[C:14]([NH:13][C:5]1[C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=[CH:7][C:6]=1[CH:10]([CH3:12])[CH3:11])=[O:34]
Reactant: [N-]=[N+]=[N-]
Reactant: CCCCCCCCCCCCn1nnc(C(Br)C(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCn1nnc(C(N)C(=O)Nc2c(C(C)C)cccc2C(C)C)n1
Temperature: 24 °C
Reaction time: 72 h
Yield: 65.9 %

Procedure:
(±)-N-(2,6-diisopropylphenyl)-2-(2-dodecyl -2H-tetrazol-5-yl)-2-bromoacetamide (1 g, 1.87 mmol) from Example 1 (e) was added to a solution containing sodium azide (0.24 g, 3.7 mmol) in ethanol (20 mL). The solution was stirred for 72 hours at 24° C. Sodium borohydride (0.07 g, 1.87 mmol) was added to the reaction mixture in one portion. The suspension was stirred for 12 hours at 24° C., then concentrated in vacuo. The resulting residue was triturated with ethyl acetate, filtered, and the filtrate was concentrated in vacuo leaving a viscous liquid. The liquid was dissolved in 10 mL of 50% ethyl acetate/ 50% hexane and purified by silica gel chromatography (elution with 50% ethyl acetate/50% hexane) to give (±)-2-amino-N-(2,6-diisopropylphenyl)-2-(2-dodecyl -2H-tetrazol-5-yl)-acetamide (0.58 g, 66%) as a colorless liquid;
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6]2[CH:7]=[C:8]([CH:11]([OH:15])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[CH3:16][C:2]1([CH3:1])[C:6]2[CH:7]=[C:8]([C:11](=[O:15])[CH:12]([CH3:13])[CH3:14])[CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1
Reactant: CC(C)C(O)c1ccc2c(c1)C(C)(C)CO2
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)C(=O)c1ccc2c(c1)C(C)(C)CO2
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.1 %

Procedure:
To a solution of 1-(3,3-dimethyl-2,3-dihydro-benzofuran-5-yl)-2-methyl-propan-1-ol (example 1e) (1.13 g, 5.15 mmol) in dry dichloromethane (20 mL) was added at room temperature pyridinium chlorochromate (1.33 g, 6.18 mmol). The reaction mixture was stirred for 2 hours at room temperature then filtered over celite. Water was added and the layers separated. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (5% ethyl acetate in hexane) to give 530 mg of 1-(3,3-dimethyl-2,3-dihydro-benzofuran-5-yl)-2-methyl-propan-1-one (47%). 1H NMR (300 MHz; CDCl3): δ 1.21 (d, J=7.2 Hz, 6H), 1.38 (s, 6H), 3.52 (m, 1H), 4.32 (s, 2H), 6.80 (d, J=7.5 Hz, 1H), 7.80 (m, 2H).
Reaction SMILES: [OH-].[Na+].[CH:3]1([N:6]2[C:14]3[C:9](=[C:10]([C:20]4[NH:24][N:23]=[N:22][N:21]=4)[CH:11]=[C:12]([C:15]([O:17]CC)=[O:16])[CH:13]=3)[CH:8]=[CH:7]2)[CH2:5][CH2:4]1.Cl>CO>[CH:3]1([N:6]2[C:14]3[C:9](=[C:10]([C:20]4[NH:24][N:23]=[N:22][N:21]=4)[CH:11]=[C:12]([C:15]([OH:17])=[O:16])[CH:13]=3)[CH:8]=[CH:7]2)[CH2:4][CH2:5]1
Reactant: CCOC(=O)c1cc(-c2nnn[nH]2)c2ccn(C3CC3)c2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1cc(-c2nnn[nH]2)c2ccn(C3CC3)c2c1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
In a 500-mL egg plant-type flask, aqueous 5 N sodium hydroxide solution (11 mL, 55 mmol) was added to an MeOH solution (70 mL) of ethyl 1-cyclopropyl-4-(tetrazol-5-yl)-1H-indole-6-carboxylate (5.40 g), and stirred at 60° C. for 8 hours. The reaction solution was left cooled, aqueous 5 N hydrochloric acid solution (12 mL) was added thereto, and the formed precipitate was taken out through filtration. This was washed with water and dried under reduced pressure to obtain the title compound as a colorless solid.
Reaction SMILES: CC(C)[C@@H](N1CC2C(=CC=C(C3C=CC(NC(NC4C=CC=C(C(F)(F)F)C=4)=O)=CC=3)C=2)C1=O)C(O)=O.[O:38]=[C:39]1[C:47]2[C:42](=[CH:43][C:44]([C:48]3[CH:53]=[CH:52][C:51]([NH:54][C:55]([NH:57][C:58]4[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:67])([F:66])[F:65])[CH:59]=4)=[O:56])=[CH:50][CH:49]=3)=[CH:45][CH:46]=2)[CH2:41][N:40]1[C@@H:68]([C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)[C:69]([O:71]C)=[O:70]>>[O:38]=[C:39]1[C:47]2[C:42](=[CH:43][C:44]([C:48]3[CH:53]=[CH:52][C:51]([NH:54][C:55]([NH:57][C:58]4[CH:63]=[CH:62][CH:61]=[C:60]([C:64]([F:66])([F:65])[F:67])[CH:59]=4)=[O:56])=[CH:50][CH:49]=3)=[CH:45][CH:46]=2)[CH2:41][N:40]1[C@@H:68]([C:73]1[CH:74]=[CH:75][CH:76]=[CH:77][CH:78]=1)[C:69]([OH:71])=[O:70]
Reactant: COC(=O)[C@H](c1ccccc1)N1Cc2cc(-c3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)ccc2C1=O
Agent: CC(C)[C@H](C(=O)O)N1Cc2cc(-c3ccc(NC(=O)Nc4cccc(C(F)(F)F)c4)cc3)ccc2C1=O
Product: O=C(Nc1ccc(-c2ccc3c(c2)CN([C@H](C(=O)O)c2ccccc2)C3=O)cc1)Nc1cccc(C(F)(F)F)c1
Yield: 92 %

Procedure:
The compound of example 373 was prepared analogous to the compound of example 361 by hydrolysis of the compound of example 372.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH:5]=O.Cl.[NH2:12][OH:13].C(=O)([O-])[O-].[Na+].[Na+]>CO.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[CH:5]=[N:12][OH:13]
Reactant: NO
Reactant: Cc1ccc(C=O)cc1Br
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cc1ccc(C=NO)cc1Br
Temperature: 0 °C
Reaction time: 1 h
Yield: 79.4 %

Procedure:
To a stirred suspension of 3-bromo-4-methylbenzaldehyde (1.0 g, 5 mmol, 1.0 eq) in methanol (50 mL) was added a solution hydroxylamine hydrochloride (434 mg, 6.3 mmol, 1.2 eq) in water (2 mL) at room temperature. The resulting solution was cooled to 0° C. and then treated with an aqueous solution of sodium carbonate (2M, 2 mL). After stirring for 1 h at room temperature, the solvent was removed under vacuum. The residue was taken into ethyl acetate (20 mL) and water (10 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic layers were washed with brine (15 mL), dried (Na2SO4) and filtered. The filtrate was evaporated under vacuum to afford 0.85 g of the title product as a white solid. 1HNMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 7.87 (s, 1H, D2O exchangeable) 7.76 (d, J=1.5 Hz, 1H), 7.43 (dd, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 2.44 (s, 3H); ESI-MS (m/z) 214, 216 [(MH)+, Br79,81].
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:16])[CH:14]=3)[N:9]3[CH2:17][CH2:18][CH2:19][CH2:20][C:8]=23)=[CH:3][CH:2]=1.[CH2:21]([O:23][C:24](=[O:29])[C:25](Br)([CH3:27])[CH3:26])[CH3:22]>>[CH2:21]([O:23][C:24](=[O:29])[C:25]([O:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]1[CH2:17][CH2:18][CH2:19][CH2:20][C:8]1=[C:7]2[C:4]1[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=1)([CH3:27])[CH3:26])[CH3:22]
Reactant: Oc1ccc2c(c1)c(-c1ccncc1)c1n2CCCC1
Reactant: CCOC(=O)C(C)(C)Br
Product: CCOC(=O)C(C)(C)Oc1ccc2c(c1)c(-c1ccncc1)c1n2CCCC1

Procedure:
The above compound was prepared from 6,7,8,9-tetrahydro-10-(4-pyridyl)-pyrido[1,2-a]indole-2-ol and 2-bromo-2-methyl-propanoic acid ethylester using a procedure analogous to that of Example 10.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH:20]([C:22]3[CH:23]=[N:24][C:25]([N:28]4[Si](C)(C)CC[Si]4(C)C)=[CH:26][CH:27]=3)O)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.NC1N=CC(C(C2C3C(=NC=C(Cl)C=3)N(S(C3C=CC=CC=3)(=O)=O)C=2)O)=CC=1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Cl:19])[CH:18]=[C:13]3[C:12]([CH2:20][C:22]3[CH:27]=[CH:26][C:25]([NH2:28])=[N:24][CH:23]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C[Si]1(C)CC[Si](C)(C)N1c1ccc(C(O)c2cn(S(=O)(=O)c3ccccc3)c3ncc(Cl)cc23)cn1
Agent: CC[SiH](CC)CC
Agent: Nc1ccc(C(O)c2cn(S(=O)(=O)c3ccccc3)c3ncc(Cl)cc23)cn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1ccc(Cc2cn(S(=O)(=O)c3ccccc3)c3ncc(Cl)cc23)cn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To (1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-[6-(2,2,5,5-tetramethyl-[1,2,5]azadisilolidin-1-yl)-pyridin-3-yl]-methanol and (6-amino-pyridin-3-yl)-(1-benzenesulfonyl-5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol (118, 119, 1.70/1.25 g mix, 2.41 mmol) in 25.0 mL of dichloromethane, triethylsilane (3.00 mL, 18.8 mmol) and trifluoroacetic acid (1.50 mL, 19.5 mmol) were added and the reaction stirred at room temperature overnight. The reaction was concentrated under vacuum, combined with aqueous potassium carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane to provide the desired compound (120, 0.70 g).
Reaction SMILES: [N:1]([CH2:4][CH:5]([C:13]1([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]1=[O:26])[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[N+]=[N-]>[Pd].CCO>[NH2:1][CH2:4][CH:5]([C:13]1([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:14]1=[O:26])[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7]
Reactant: CC(C)CC1(C(CN=[N+]=[N-])C(=O)OC(C)(C)C)CCN(CCc2ccccc2)C1=O
Agent: [Pd]
Solvent: CCO
Product: CC(C)CC1(C(CN)C(=O)OC(C)(C)C)CCN(CCc2ccccc2)C1=O
Reaction time: 16 h
Yield: 58.7 %

Procedure:
A mixture of tert-butyl α-(1-azidomethyl)-3-(2-methylpropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetate (648 mg, 1.56 mmol) and 10% palladium on carbon (163 mg) in EtOH (25 mL) is hydrogenated at 30 psi in a Parr flask for 16 hours. The mixture is filtered, rinsing the residual solids with MeOH and CH2 Cl2. The filtrate is concentrated and purified by silica gel chromatography (15 g SG; EtOAc, 15% MeOH/EtOAc) to provide 356 mg (57%) of the title compound as a partially crystalline solid:
Reaction SMILES: F[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.[CH2:23]([NH2:25])[CH3:24].O>CS(C)=O>[CH2:23]([NH:25][C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2)[CH3:24]
Reactant: CCN
Reactant: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1F
Solvent: O
Solvent: CS(C)=O
Product: CCNc1nc2c(-c3cc4c([nH]3)CCNC4=O)cccc2nc1C
Temperature: 80 °C
Reaction time: 2 h

Procedure:
Prepared according to Example 127, using 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 40 mg, 0.135 mmol), 70% v/v ethanamine in water (26.1 mg, 0.405 mmol, Sigma Aldrich), and DMSO (1.4 mL) and stirring at 80° C. for 2 h. Purification by high throughput parallel purification (Rilas Technologies, Woburn, Mass.) provided 2-(3-(ethylamino)-2-methyl-5-quinoxalinyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one. 1H NMR (DMSO-d6) δ: 12.23 (br. s, 1H), 7.84-7.89 (m, 1H), 7.50-7.56 (m, 1H), 7.26-7.33 (m, 2H), 7.06-7.11 (m, 1H), 6.93 (br. s, 1H), 3.48-3.58 (m, 2H), 3.38-3.45 (m, 2H), 2.82-2.89 (m, 2H), 2.50 (s, 3H), 1.30 (t, J=1.0 Hz, 3H). m/z (ESI, +ve) 322.1 (M+H)+.