Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:45]=[CH:44][C:6]2[N:7]([CH2:30][C:31]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=[CH:33][C:32]=3[CH:41]3[CH2:43][CH2:42]3)[C:8](=[O:29])[C@@H:9]([NH:21]C(=O)OC(C)(C)C)[C@H:10]([CH3:20])[N:11]([C:12]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[O:13])[C:5]=2[CH:4]=1)#[N:2].[ClH:46]>O1CCOCC1.CCOCC>[ClH:46].[ClH:46].[NH2:21][C@@H:9]1[C:8](=[O:29])[N:7]([CH2:30][C:31]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[N:34]=[CH:33][C:32]=2[CH:41]2[CH2:43][CH2:42]2)[C:6]2[CH:44]=[CH:45][C:3]([C:1]#[N:2])=[CH:4][C:5]=2[N:11]([C:12]([CH:14]2[CH2:15][CH2:16][O:17][CH2:18][CH2:19]2)=[O:13])[C@H:10]1[CH3:20]
Reactant: C[C@H]1[C@H](NC(=O)OC(C)(C)C)C(=O)N(Cc2c(C3CC3)cnc3ccccc23)c2ccc(C#N)cc2N1C(=O)C1CCOCC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Product: C[C@H]1[C@H](N)C(=O)N(Cc2c(C3CC3)cnc3ccccc23)c2ccc(C#N)cc2N1C(=O)C1CCOCC1
Yield: 91 %

Procedure:
A rt solution of tert-butyl(3S,4S)-7-cyano-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (69 mg, 113 μmol) in 4 M HCl in dioxane (566 μl) was stirred for 2 h. The reaction was diluted with Et2O and the solids were collected by vacuum filtration to provide (3S,4S)-3-amino-1-((3-cyclopropylquinolin-4-yl)methyl)-4-methyl-2-oxo-5-(tetrahydro-2H-pyran-4-carbonyl)-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepine-7-carbonitrile dihydrochloride (60 mg, 91%) as a white solid.
Reaction SMILES: Cl.[C:2]1([N:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)N)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][CH:17]([CH3:45])[C:18]([NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]2[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][CH2:36][C:37](=O)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:29][CH2:28]2)[CH:22]=1)=[O:19].C([O-])([O-])=O.[K+].[K+]>O.[Cl-].[Cl-].[Zn+2]>[C:2]1([N:8]2[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:36]([CH2:35][CH2:34][CH2:33][N:30]3[CH2:31][CH2:32][CH:27]([C:23]4[CH:22]=[C:21]([NH:20][C:18](=[O:19])[CH:17]([CH3:45])[CH3:16])[CH:26]=[CH:25][CH:24]=4)[CH2:28][CH2:29]3)=[C:37]2[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3ccccc3)CC2)c1
Reactant: NN(c1ccccc1)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4ccccc4)n(-c4ccccc4)c4ccccc34)CC2)c1
Temperature: 80 °C
Yield: 20.4 %

Procedure:
A mixture of 1,1-diphenylhydrazine hydrochloride (10.3 mg, 0.0470 mmol), 2-methyl-N-(3-[1-(5-oxo-5-phenylpentyl)-4-piperidinyl]phenyl}propanamide (14.7 mg, 0.0362 mmol), ZnCl2 (14.85 mg, 0.109 mmol), and HOAC (0.5 mL) was heated for 4 h at 80° C. The resulting crude mixture was diluted with water (10 mL), the aqueous layer was neutralized with saturated K2CO3 and extracted with CH2Cl2 (3×20 mL). The combined organic layers were concentrated in vacuo and the residue was purified by preparative TLC using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product N-(3-{1-[3-(1,2-diphenyl-1H-indol-3-yl)propyl]-4-piperidinyl}phenyl)-2-methylpropanamide (4.1 mg, 37%). 1H NMR (400 MHz, CDCl3) δ 7.71-7.65 (m, 1H), 7.42 (d, 1H, J=7.4 Hz), 7.39 (s, 1H), 7.36-7.15 (m, 15H), 6.94 (d, 1H, J=7.8 Hz), 3.12 (d, 2H, J=11.2 Hz), 2.90 (t, 2H, J=7.8 Hz), 2.59-2.45 (m, 3H), 2.19-1.91 (m, 7H), 1.82 (d, 2H, J=13.5 Hz), 1.24 (d, 6H, J=6.9 Hz); ESMS m/e: 555.3 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11](=[C:14]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]#[N:25])[CH:19]=2)SC)[C:12]#[N:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH:26]1([NH2:31])[CH2:30][CH2:29][CH2:28][CH2:27]1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11](=[C:14]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[NH:31][CH:26]2[CH2:30][CH2:29][CH2:28][CH2:27]2)[C:12]#[N:13])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: NC1CCCC1
Reactant: CSC(Nc1cccc(C#N)c1)=C(C#N)S(=O)(=O)c1ccc(Cl)cc1
Product: N#CC(=C(Nc1cccc(C#N)c1)NC1CCCC1)S(=O)(=O)c1ccc(Cl)cc1
Yield: 16 %

Procedure:
2-(4-Chlorophenylsulfonyl)-3-(3-cyanophenylamino)-3-methylsulfanyl-2-propenenitrile (0.300 g, 0.6 mmol) was stirred in cyclopentylamine (1 ml) for 48 h at 100° C. under nitrogen in a sealed flask. Work up as described in Example 1, 2) gave 51 mg (16%) of the title compound as light brown crystals. 1H NMR (200 MHz, CDCl3): δ=1.43-1.54 (m, 4H), 1.68-1.78 (m, 4H), 3.64 (sextet, 1H), 7.07 (d, 1H), 7.21 (s, 1H), 7.40-7.55 (m, 6H), 7.77 (dd, 2H)
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([NH2:17])[C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5]2)[CH2:3][CH2:2]1.[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][NH:26][CH2:27]2.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]2[C:24]=1[CH2:25][N:26]([C:11]1[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5][N:4]3[CH:1]3[CH2:2][CH2:3]3)=[C:9]([NH2:17])[C:10]=1[F:16])[CH2:27]2
Reactant: Fc1cccc2c1CNC2
Reactant: Nc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: Nc1c(F)c(N2Cc3cccc(F)c3C2)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Yield: 21.2 %

Procedure:
200 mg of 1-cyclopropyl-5-amino-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 101 mg of 4-fluoroisoindoline, 200 mg of DBU, and 1.5 ml of anhydrous DMF were processed in the same manner as in Example 20 to produce 59 mg of the target compound.
Reaction SMILES: [C:1]([CH2:3][C:4](OCC)=[O:5])#[N:2].[NH2:9][C:10]([NH2:12])=[S:11].[Na].OC1C=CC=CN=1>C(O)(=O)C.O.CO>[NH2:2][C:1]1[CH:3]=[C:4]([OH:5])[N:12]=[C:10]([SH:11])[N:9]=1
Reactant: NC(N)=S
Reactant: CCOC(=O)CC#N
Agent: Oc1ccccn1
Agent: [Na]
Solvent: O
Solvent: CC(=O)O
Solvent: CO
Product: Nc1cc(O)nc(S)n1
Yield: 82 %

Procedure:
0.57 g. of ethyl cyanoacetate and 0.38 g. of thiourea are heated under reflux in 3 ml. of methanol in the presence of 1.17 g. of the sodium salt of 2-hydroxypyridine. After completion of reaction, 4 ml. of water is added, and the solution is neutralized with 0.58 ml. of acetic acid, to deposit the desired monohydrate crystals. Yield: 82%. The ultraviolet absorption spectrum agrees closely with the literature values.
Reaction SMILES: C1(CC(=O)CC2C=CC=C(C(F)(F)F)C=2)C=CC=CC=1.C(OCC)=O.Cl.C(N)C=C.[CH2:31]([N:34]1[CH:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([C:46]([F:49])([F:48])[F:47])[CH:41]=2)[C:37](=[O:50])[C:36]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[CH:35]1)[CH:32]=[CH2:33].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH2:31]([N:34]1[CH2:39][CH:38]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([C:46]([F:48])([F:47])[F:49])[CH:41]=2)[C:37](=[O:50])[CH:36]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH2:35]1)[CH:32]=[CH2:33]
Reactant: C=CCn1cc(-c2ccccc2)c(=O)c(-c2cccc(C(F)(F)F)c2)c1
Agent: Cl
Agent: O=C(Cc1ccccc1)Cc1cccc(C(F)(F)F)c1
Agent: [Al+3]
Solvent: CCOC=O
Solvent: C=CCN
Product: C=CCN1CC(c2ccccc2)C(=O)C(c2cccc(C(F)(F)F)c2)C1

Procedure:
Twenty g. of 1-phenyl-3-(3-trifluoromethylphenyl)-2-propanone was reacted with ethyl formate and allylamine hydrochloride as described in Examples 1-3 to obtain 10.8 g. of 1-allyl-3-phenyl-5-(3-trifluoromethylphenyl)-4(1H)-pyridinone, which was reacted with 2 g. of lithium aluminum hydride as described in Examples 1-3. The reaction mixture was worked up and chromatographed as described in the examples above to obtain 1.2 g. of the products of Examples 33 and 34 as a mixture. The compounds were identified by mass spectroscopy, which showed an indicated molecular weight of 357. A yield of 1.0 g. of the compound of Example 35 was obtained, which showed a mass spectroscopy molecular weight of 359.
Reaction SMILES: C(OC([N:11]1[C:15]([CH:16]([CH3:18])[CH3:17])=[C:14]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:13]([O:26][C@@H:27]2[O:53][C@H:52]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:60])([CH3:59])[CH3:58])[C@@H:44]([O:45][C:46](=[O:51])[C:47]([CH3:50])([CH3:49])[CH3:48])[C@H:36]([O:37][C:38](=[O:43])[C:39]([CH3:42])([CH3:41])[CH3:40])[C@H:28]2[O:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:33])[CH3:32])=[N:12]1)=O)C1C=CC=CC=1>CO.[Pd]>[CH2:19]([C:14]1[C:13]([O:26][C@@H:27]2[O:53][C@H:52]([CH2:54][O:55][C:56](=[O:61])[C:57]([CH3:58])([CH3:60])[CH3:59])[C@@H:44]([O:45][C:46](=[O:51])[C:47]([CH3:50])([CH3:49])[CH3:48])[C@H:36]([O:37][C:38](=[O:43])[C:39]([CH3:40])([CH3:42])[CH3:41])[C@H:28]2[O:29][C:30](=[O:35])[C:31]([CH3:34])([CH3:32])[CH3:33])=[N:12][NH:11][C:15]=1[CH:16]([CH3:18])[CH3:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)c1c(Cc2ccccc2)c(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)nn1C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC(C)c1[nH]nc(O[C@@H]2O[C@H](COC(=O)C(C)(C)C)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@H]2OC(=O)C(C)(C)C)c1Cc1ccccc1
Temperature: 25 °C
Reaction time: 13 h
Yield: 96.9 %

Procedure:
To a solution of 1-benzyloxycarbonyl-4-benzyl-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyl-oxy)-1H-pyrazole (0.228 g) in methanol (5 mL) was added 10% palladium on carbon (50% wet: 0.40 g). In addition, the mixture was stirred under a hydrogen atmosphere at room temperature for 13 hours. The insoluble materials were removed by filtration through Celite®, and the filtrate was concentrated under reduced pressure to give 4-benzyl-5-isopropyl-3-(2,3,4,6-tetra-O-pivaloyl-β-D-glucopyranosyloxy)-1H-pyrazole (0.186 g).
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[C:5]([F:11])[CH:4]=1.[B:12](OC(C)C)([O:17]C(C)C)[O:13]C(C)C.Cl>C1COCC1>[CH3:10][O:9][C:6]1[CH:7]=[CH:8][C:3]([B:12]([OH:17])[OH:13])=[CH:4][C:5]=1[F:11]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: COc1ccc(Br)cc1F
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Product: COc1ccc(B(O)O)cc1F
Yield: 78.6 %

Procedure:
Then, 9.6 g of magnesium was added to 230 ml of THF, and the solution thus formed was slowly added dropwise with 70.9 g of the 4-bromo-2-fluoroanisole obtained by the procedure mentioned above to prepare a Grignard reagent. The reagent was added dropwise to a mixture of 123.8 g of triisopropyl borate and 391 ml of THF at a temperature of -60° C. to -50° C. with stirring. After the dropping of the reagent was finished, the solution was subjected to reaction at an ambient temperature for 2 hours, added with 242 ml of a 1N-aqueous hydrochloric acid solution, subjected to further reaction for 1 hour, extracted with an ether, washed with water, and concentrated under a reduced pressure to obtain 46.2 g of 4-methoxy-3-fluorobenzene boronic acid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[CH:7]2.[CH3:11][N:12]1[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]1>>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[C:15]1[CH2:16][CH2:17][N:12]([CH3:11])[CH2:13][CH:14]=1
Reactant: Fc1cccc2cc[nH]c12
Reactant: CN1CCC(=O)CC1
Product: CN1CC=C(c2c[nH]c3c(F)cccc23)CC1
Yield: 75.1 %

Procedure:
Beginning with 0.50 gm (3.70 mMol) 7-fluoro-1H-indole and 0.91 mL (7.4 mMol) 1-methyl-4-piperidone, 0.64 gm (75%) of the title compound were recovered as a white solid.
Reaction SMILES: [N+:1]([C:4]1[N:5]([CH2:9][C@H:10]2[CH2:12][O:11]2)[CH:6]=[CH:7][N:8]=1)([O-:3])=[O:2].C(O)C.C([N:18]([CH2:21][CH3:22])CC)C>>[N:18]1([CH2:12][C@@H:10]([OH:11])[CH2:9][N:5]2[CH:6]=[CH:7][N:8]=[C:4]2[N+:1]([O-:3])=[O:2])[CH2:21][CH2:22]1
Reactant: O=[N+]([O-])c1nccn1C[C@H]1CO1
Reactant: CCN(CC)CC
Solvent: CCO
Product: O=[N+]([O-])c1nccn1C[C@H](O)CN1CC1

Procedure:
A solution of 0.3 g (1.8 mmole) of (S)-(-)-2-nitro-1-(2-oxiranyl-methyl)-1H-imidazole, 0.24 g (5.4 mmole) of 1H-aziridine, and 3.5 mL of 99:1 absolute ethanol:triethylamine is heated at reflux for 10 minutes, cooled, and concentrated. The residue is crystallized from 99:1 absolute ethanol:triethylamine to give product, mp 119.5°-121° C. [α]D25 =-28.7° [c1.15, chloroform].
Reaction SMILES: C([O:8][C:9]1[CH:37]=[CH:36][C:12]2[NH:13][C:14]([C:19]3[C:20](=[O:35])[N:21]([NH:30][CH:31]4[CH2:34][CH2:33][CH2:32]4)[C:22]4[C:27]([C:28]=3[OH:29])=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1)C1C=CC=CC=1>O1CCCC1.[Pt]=O>[CH:31]1([NH:30][N:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:28]([OH:29])=[C:19]([C:14]3[NH:13][C:12]4[CH:36]=[CH:37][C:9]([OH:8])=[CH:10][C:11]=4[S:16](=[O:17])(=[O:18])[N:15]=3)[C:20]2=[O:35])[CH2:32][CH2:33][CH2:34]1
Reactant: O=c1c(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)c(O)c2ccccc2n1NC1CCC1
Agent: O=[Pt]
Solvent: C1CCOC1
Product: O=c1c(C2=NS(=O)(=O)c3cc(O)ccc3N2)c(O)c2ccccc2n1NC1CCC1
Yield: 102.3 %

Procedure:
The product of Example 304H (0.059 g, 0.11 mmol) in tetrahydrofuran (4 mL) was reacted with platinum oxide (50 mg) under hydrogen atmosphere at 25° C. for 20 hours. The catalyst was filtered off and the filtrate evaporated to give the title compound (0.048 g, 100%). MS (ESI−) m/z 425 (M−H)−.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([OH:12])=O.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[NH:23]1[C:27]2=[N:28][CH:29]=[CH:30][CH:31]=[C:26]2[C:25](C(OCC)=O)=[N:24]1.N1C2=NC=CC=C2C(C(OC(C)C)=O)=N1>C1COCC1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][C:10]([C:25]1[C:26]2[C:27](=[N:28][CH:29]=[CH:30][CH:31]=2)[NH:23][N:24]=1)=[O:12]
Reactant: CCOC(=O)c1n[nH]c2ncccc12
Reactant: O=C(O)Cc1cccc(F)c1F
Agent: CC(C)OC(=O)c1n[nH]c2ncccc12
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C(Cc1cccc(F)c1F)c1n[nH]c2ncccc12
Yield: 91 %

Procedure:
To a solution of 2,3-difluorophenylacetic acid (236 mg, 1.4 mmol) in THF at OC was added 3.85 mL (3.85 mmol) of a solution of lithium bis-trimethylsilylamide in THF. The resulting solution was then added to solution of a 2:1 mixture of ethyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate and isopropyl 1H-pyrazolo[3,4-b]pyridine-3-carboxylate (104 mg, 0.55 mmol) in THF. The resulting mixture was heated at 75C for 3 hours. The reaction progress was monitored by TLC and HPLC and quenched with saturated NH4Cl, diluted with EtOAc and washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4 and concentrated to give 137 mg (91% yield) of 2-(2,3-difluorophenyl)-1-(1H-pyrazolo[3,4-b]pyridin-3-yl)ethanone. LC-MS Rt=3.3 min ES+ (274.0) ES− (272.1).
Reaction SMILES: [NH2:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH2:3]1.O=[C:23]([CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[C:24]([O:26][CH2:27][CH3:28])=[O:25].C(O)(=O)C.[BH]C#N.[Na]>C(O)C>[CH2:27]([O:26][C:24]([CH:23]([NH:1][CH:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH2:3]1)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[O:25])[CH3:28]
Reactant: CCCCCCCCC(=O)C(=O)OCC
Reactant: CC(C)(C)OC(=O)CN1C(=O)C(N)CSc2ccccc21
Agent: [BH]C#N
Agent: [Na]
Solvent: CC(=O)O
Solvent: CCO
Product: CCCCCCCCC(NC1CSc2ccccc2N(CC(=O)OC(C)(C)C)C1=O)C(=O)OCC
Reaction time: 3 h
Yield: 84.3 %

Procedure:
1.3 g of 3-amino-5-t-butoxycarbonylmethyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one and 3.0 g of ethyl 2-ketodecanoate were dissolved in 10 ml of ethanol. After the addition of 0.3 ml of acetic acid, the resulting mixture was stirred for 3 hours. Then, a solution of 420 mg of sodium boron cyanide hydride in 7 ml of ethanol was added dropwise thereto. After this mixture was allowed to stand overnight, it was concentrated under reduced pressure and the residue was dissolved in ethyl acetate. The solution was washed with water, dried and then concentrated. The residue was purified by silica gel column chromatography using a 7:1 mixture of benzene and ethyl acetate as the eluent. Thus, there was obtained 1.8 g of the desired compound in the form of an oily material.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[CH:18][C:19]([F:23])=[CH:20][CH:21]=3)[N:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:15]=2[CH2:30][CH3:31])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:30]([C:15]1[N:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:17]2[C:22]([C:14]=1[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[CH3:31]
Reactant: CCc1c(C2CCN(C(=O)OC(C)(C)C)CC2)c2ccc(F)cc2n1-c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCc1c(C2CCNCC2)c2ccc(F)cc2n1-c1ccccc1
Reaction time: 15 h
Yield: 76.4 %

Procedure:
To a stirred solution of 4-(2-ethyl-6-fluoro-1-phenyl-1H-indol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester (0.12 g) in DCM (20 ml) at r.t., is added trifluoroacetic acid (0.5 ml). After 15 h, the mixture is concentrated in vacuo. Flash chromatography (DCM:MeOH, gradient elution) of the resulting liquid gives 70 mg pure product (57%, TFA salt) as a beige solid after trituration with diethylether.
Reaction SMILES: FC(F)(F)C(O)=O.[NH2:8][CH2:9][C:10]1[CH:34]=[C:33]([F:35])[CH:32]=[CH:31][C:11]=1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([CH3:20])[N:17]([C:21]2[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=2[F:28])[C:16](=[O:29])[C:15]=1[Br:30].C(N(CC)CC)C.[CH3:43][O:44][C:45](Cl)=[O:46]>CC(N(C)C)=O>[Br:30][C:15]1[C:16](=[O:29])[N:17]([C:21]2[C:22]([F:28])=[CH:23][CH:24]=[CH:25][C:26]=2[F:27])[C:18]([CH3:20])=[CH:19][C:14]=1[O:13][CH2:12][C:11]1[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:10]=1[CH2:9][NH:8][C:45](=[O:46])[O:44][CH3:43]
Reactant: Cc1cc(OCc2ccc(F)cc2CN)c(Br)c(=O)n1-c1c(F)cccc1F
Reactant: COC(=O)Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC(=O)N(C)C
Product: COC(=O)NCc1cc(F)ccc1COc1cc(C)n(-c2c(F)cccc2F)c(=O)c1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
To solution of 4-{[2-(aminomethyl)-4-fluorobenzyl]oxy}-3-bromo-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one trifluoroacetate (0.12 g, 0.00021 mol) in dimethylacetamide (2.0 mL) at 0° C., was added triethylamine (0.06 mL, 0.00043 mol) followed by the addition of methylchloroformate (0.05 mL). The reaction mixture was stirred at room temperature for 30 min under argon atmosphere. Dimethylacetamide was distilled in vacuo and the residue was partitioned between dichloromethane (10 mL) and 5% citric acid (10 mL). The organic phase was washed with water, dried (Na2SO4) and concentrated to dryness. The resulting residue was purified by flash chromatography (60% EtOAc in hexane) to afford the title compound (0.09 g, 75%) as a white amorphous powder: 1H NMR (DMSO-d6/400 MHz) δ 7.68 (m, 1H), 7.62 (m, 1H), 7.59 (m, 1H) 7.38 (m, 2H), 7.115 (m, 2H), 6.78 (s, 1H), 5.38 (s, 2H), 4.31 (d, 2H, J=6.0 Hz), 3.53 (s, 3H), and 2.03 (s, 3H); 19F NMR (DMSO-d6/400 MHz) δ−113.77 (m), and −120.33 (m); ES-HRMS m/z 511.0508 (M+H C22H19N2O4F3Br requires 511.0475).