Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: NC1C=CNN=1.O/[CH:8]=[C:9]1\[C:10](=[O:18])[NH:11][C:12]2[C:17]\1=[CH:16][CH:15]=[CH:14][CH:13]=2.[CH3:19][N:20]([CH3:33])[C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[C:29]([NH2:32])[NH:30][N:31]=2)=[CH:23][CH:22]=1>O1CCCC1>[CH3:19][N:20]([CH3:33])[C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:28]=[C:29]([NH:32][CH:8]=[C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[NH:11][C:10]3=[O:18])[NH:30][N:31]=2)=[CH:25][CH:26]=1
Reactant: CN(C)c1ccc(-c2cc(N)[nH]n2)cc1
Reactant: O=C1Nc2ccccc2/C1=C/O
Agent: Nc1cc[nH]n1
Solvent: C1CCOC1
Product: CN(C)c1ccc(-c2cc(NC=C3C(=O)Nc4ccccc43)[nH]n2)cc1

Procedure:
The named compound is prepared by substituting 5-(4-dimethylamino-phenyl)-2H-pyrazol-3-ylamine for 3-aminopyrazole in the reaction of Example 1. Specifically, E & Z-3-[(hydroxy)-methylene]-1,3-dihydro-indol-2-one (0.100 gms.) is reacted with 0.2543 gms. 5-(4-dimethylamino-phenyl)-2H-pyrazol-3-ylamine by refluxing in tetrahydrofuran (2.0 mL) overnight.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[CH:8]=[C:9]([C:11]3[O:12][CH:13]=[CH:14][N:15]=3)[NH:10][C:5]2=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CN(C=O)C>[CH2:22]([N:10]1[C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:8]=[C:9]1[C:11]1[O:12][CH:13]=[CH:14][N:15]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: BrCc1ccccc1
Reactant: Clc1ccc2[nH]c(-c3ncco3)cc2n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Clc1ccc2c(cc(-c3ncco3)n2Cc2ccccc2)n1

Procedure:
To a well stirred mixture of 5-chloro-2-(1,3-oxazol-2-yl)-1H-pyrrolo[3,2-b]pyridine (0.39 g, 1.8 mmol, from Step 2) in DMF (8 mL) was added Cs2CO3 (1.7 g, 5.3 mmol) and benzyl bromide (0.21 mL, 1.8 mmol, Aldrich). After stirring overnight, the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with an additional two portions of EtOAc. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. The resulting light yellow crystalline solid was used directly in Step 4. LCMS (M+H)+: 310.1/312.1.
Reaction SMILES: [C:1]1(=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=3)[C:6]=2[C:25]([O:27]CC)=[O:26])[CH2:3][CH2:2]1.[OH-].[Na+]>O1CCCC1>[C:1]1(=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=3)[C:6]=2[C:25]([OH:27])=[O:26])[CH2:3][CH2:2]1
Reactant: CCOC(=O)c1c(C=C2CC2)c2ccccc2n1Cc1cccc(C(F)(F)F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1c(C=C2CC2)c2ccccc2n1Cc1cccc(C(F)(F)F)c1
Yield: 57 %

Procedure:
The compound was prepared from ethyl 3-(cyclopropylidenemethyl)-1-[3-(trifluoromethyl)benzyl]-1H-indole-2-carboxylate (Example 182) using the method described in Example 229, except 6N aqueous sodium hydroxide solution was used with tetrahydrofuran as a co-solvent. Flash chromatography of the residue over silica gel using 50% ethyl acetate/hexane gave the title compound (57%) as a pale yellow solid (mp=148-150° C). The product had: 1H NMR (300 MHz, acetone-d6) δ 11.70 (s, 1 H), 8.16 (d, 1 H), 7.70 (s, 1 H), 7.56-7.46 (m, 4 H), 7.35-7.27 (m, 2 H), 7.19-7.15 (m, 1 H), 5.98 (s, 2 H), 1.58-1.53 (m, 2 H), 1.33-1.28 (m, 2 H); mass spectroscopy gave MH+=372.1 (calcd exact mass for C21H16F3NH2=371.11).
Reaction SMILES: C1(C(C2C=CC3[O:21][C:22]([F:25])([F:24])[O:23]C=3C=2)C2C3C(=C(CSC)C=CC=3)NC=2)CC1.Cl[C:29]1[CH:34]=[CH:33][C:32]([CH:35]([CH:50]2[CH2:52][CH2:51]2)[C:36]2[C:44]3[C:39](=[C:40]([CH2:45][S:46]([CH3:49])(=[O:48])=[O:47])[CH:41]=[CH:42][CH:43]=3)[NH:38][CH:37]=2)=[CH:31][CH:30]=1>>[CH:50]1([CH:35]([C:32]2[CH:33]=[CH:34][C:29]3[O:21][C:22]([F:25])([F:24])[O:23][C:30]=3[CH:31]=2)[C:36]2[C:44]3[C:39](=[C:40]([CH2:45][S:46]([CH3:49])(=[O:48])=[O:47])[CH:41]=[CH:42][CH:43]=3)[NH:38][CH:37]=2)[CH2:52][CH2:51]1
Reactant: CSCc1cccc2c(C(c3ccc4c(c3)OC(F)(F)O4)C3CC3)c[nH]c12
Reactant: CS(=O)(=O)Cc1cccc2c(C(c3ccc(Cl)cc3)C3CC3)c[nH]c12
Product: CS(=O)(=O)Cc1cccc2c(C(c3ccc4c(c3)OC(F)(F)O4)C3CC3)c[nH]c12

Procedure:
The title compound was prepared starting from 500 mg (1.29 mmol) of the compound from Example 231 in analogy to the synthesis of the compound from Example 249. A difference was that the reaction solution was washed with saturated aqueous sodium bicarbonate solution before purification. 311 mg (57% of theory) of the target compound were obtained.
Reaction SMILES: Br[C:2](=[CH2:22])[CH2:3][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([Zn][CH2:72][CH3:73])C>C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:22]=[C:2]([CH2:72][CH3:73])[CH2:3][C:4]1([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:6][CH2:5]1
Reactant: C=C(Br)CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1
Reactant: CC[Zn]CC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: C1CCOC1
Product: C=C(CC)CC1(C(=O)OCC)CCN(C(=O)OC(C)(C)C)CC1
Temperature: 100 °C

Procedure:
To a solution of 1-tert-butyl 4-ethyl 4-(2-bromoallyl)piperidine-1,4-dicarboxylate (5.0 g, 13.3 mmol) in THF (80 mL) in a sealed tube was added BINAP (3.31 g, 5.32 mmol), diethylzinc (15.95 mL, 15.95 mmol) and Pd(OAc)2 (0.597 g, 2.66 mmol) and the resulting mixture was degassed and heated for 16 hours at 100° C. The reaction mixture was evaporated to remove solvent under reduced pressure and the crude product was purified by silica gel column chromatography (RediSep 220 g Gold column) using (0-30) % EtOAc/Hexanes as mobile phase and the title compound was isolated.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:19]=[CH:18][C:10]2[N:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[N:12]=[N:13][C:9]=2[C:8]=1[Cl:20])(=O)=O.CC1(C)C(C)(C)OB([C:31]2[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH:32]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)(O)[O-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.O1CCOCC1>[Cl:20][C:8]1[C:9]2[N:13]=[N:12][N:11]([CH2:14][CH:15]3[CH2:17][CH2:16]3)[C:10]=2[CH:18]=[CH:19][C:7]=1[C:31]1[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH:32]=1
Reactant: COC(=O)C1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: O=S(=O)(Oc1ccc2c(nnn2CC2CC2)c1Cl)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: O=P([O-])([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: COC(=O)C1CC=C(c2ccc3c(nnn3CC3CC3)c2Cl)CC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-yl trifluoromethanesulfonate (0.22 g, 0.62 mmol), methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-3-ene-1-carboxylate (0.21 g, 0.77 mmol, 1.25 equiv), potassium phosphate (0.39 g, 1.8 mmol, 3 equiv) and tetrakis(triphenylphosphine)palladium(0) (71 mg, 0.062 mmol, 0.1 equiv) were combined in a degassed mixture of dioxane (5 mL) and water (0.5 mL) and placed into a preheated oil bath at 90° C. for 90 minutes. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (75 mL, aqueous saturated) and extracted with ethyl acetate (2×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 25:75; hexanes:ethyl acetate), providing the titled compound as a colorless oil: 1H-NMR (400 MHz, d6-DMSO) δ 7.88 (1H, d, J=8.5 Hz), 7.41 (1H, d, J=8.5 Hz), 5.77-5.74 (1H, m), 4.61 (2H, d, J=7.7 Hz), 3.66 (3H, s), 3.37-3.32 (2H, m), 2.75-2.69 (1H, m), 2.49-2.30 (2H, m), 2.11-2.05 (1H, m), 1.84-1.76 (1H, m), 1.41-1.33 (1H, m), 0.57-0.53 (2H, m), 0.49-0.45 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 346.1316 [(M+H)+; calculated for C18H21ClN3O2: 346.1317].
Reaction SMILES: [F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][C:8]2[CH:18]=[CH:17][C:11]([CH:12]=[CH:13][C:14]([O-])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:24])=O>>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][C:8]2[CH:18]=[CH:17][C:11]([CH:12]=[CH:13][C:14]([Cl:24])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: O=C([O-])C=Cc1ccc(OCc2ccc(F)cc2)cc1
Reactant: O=C(Cl)C(=O)Cl
Product: O=C(Cl)C=Cc1ccc(OCc2ccc(F)cc2)cc1

Procedure:
7.34 g (0.027 mol) of 4-(4-fluorobenzyloxy)cinnamate and 15.0 ml of oxalyl chloride were placed in a 100 ml flask that was provided with a cooling tube, and allowed to react for 4 hours at 70° C. The excess oxalyl chloride was removed under reduced pressure, to obtain 4-(4-fluorobenzyloxy)cinnamoyl chloride. After confirming the compound's structure with IR and NMR, it was immediately used in the following reaction.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11](C(OCC(Cl)(Cl)Cl)=O)[CH2:10][CH:9]2[O:22][CH2:23][C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=2)=[CH:4][CH:3]=1>C(O)(=O)C.O.[Zn]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[O:22][CH2:23][C:24]2[CH:33]=[CH:32][C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:25]=2)=[CH:4][CH:3]=1
Reactant: O=C(OCC(Cl)(Cl)Cl)N1CCC(c2ccc(Cl)cc2)C(OCc2ccc3ccccc3c2)C1
Agent: [Zn]
Solvent: O
Solvent: CC(=O)O
Product: Clc1ccc(C2CCNCC2OCc2ccc3ccccc3c2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 74.6 %

Procedure:
A suspension of 0.420 g (0.8 mmol) of 2,2,2-trichloroethyl 4-(4-chloro-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate and 300 mg of zinc in 10 ml of acetic acid was stirred at room temperature for 12 hours. The reaction solution was diluted with 40 ml of water and extracted four times with 30 ml of methylene chloride. The organic phase was washed twice with 40 ml of 1N sodium hydroxide solution each time, dried over sodium sulphate, filtered and evaporated. The residue was chromatographed on silica gel using a 9:1 mixture of methylene chloride and methanol as the eluent. There was obtained 0.210 g (74% of theory) of (3RS,4RS)-4-(4-chloro-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine, MS: 210 (M-C11H9)+, which was converted into the hydrochloride of m.p. 159-161° C. (dec.) with a solution of hydrogen chloride in methanol.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=O)=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.Cl.C[C@H]1NCC[N:27](C(=O)C2C=CC=CC=2)C1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C)S(N)(=O)=O.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O.CN(C1C=CN=CC=1)C.CC(N(C)C)=O.C(N(CC)CC)C>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH2:27])=[O:21])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc2cc3n(c2c1)CC=Cc1ccccc1-3
Reactant: C[C@@H]1CN(C(=O)c2ccccc2)CCN1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN(C)S(N)(=O)=O
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: NC(=O)c1ccc2cc3n(c2c1)CC=Cc1ccccc1-3
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (200 mg, 0.48 mmol), 3(R)-methyl-1-benzoylpiperazine hydrochloride (130 mg, 0.58 mmol) and triethylamine (0.20 mL) in DMF (3 mL) was added HATU (220 mg, 0.58 mmol). The reaction mixture was stirred at rt for 1 h, diluted with H2O (˜5 mL) stirred for 30 min, and the solids (290 mg) collected by filtration and flushed with H2O. The crude solids were dissolved into MeOH/THF (1:1, 4 mL) and treated with 1M aqueous NaOH (0.75 mL). The reaction mixture was stirred and heated at 80° C. with microwave irradiation for 15 min in a sealed tube. The clear solution was diluted with H2O (5 mL), neutralized with 1M aqueous HCl (0.75 mL) and concentrated to remove organic solvents. The resultant solids (257 mg) were collected by filtration and washed with H2O. To a stirred solution of the crude solids (145 mg, 56% of total collected, ˜0.25 mmol), N,N-dimethylsulfamide (155 mg, 1.25 mmol) and DMAP (150 mg, 1.25 mmol) in dimethylacetamide (2 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (190 mg, 1.0 mmol). The reaction solution was stirred at 50° C. for 2 h, diluted with water (5 mL) and the resulting solids were collected by filtration. The mother liquor was concentrated and the solids and the mother liquor were independently purified by preparative HPLC (MeOH/2O with NH4OAc buffer) to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 6-[[(2R)-4-benzoyl-2-methyl-1-piperazinyl]carbonyl]-13-cyclohexyl-N-[(dimethylamino)sulfonyl] (79 mg total, 52 mg from solids and 27 mg from mother liquor, 0.11 mol, 42% over 3 steps) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.21 (s, 1H), 7.88 (d, J=8.6 Hz, 1H), 7.60-7.44 (m, 4H), 7.43-7.32 (m, 6H), 6.82 (br s, 1H), 5.21 (br s, 1H), 4.34 (br s, 1H), 4.58-3.34 (m, 7H), 3.06 (s, 6H), 2.87-2.78(m, 1H), 2.12-1.00 (m, 13H). LCMS: m/e 692 (M−H)−, ret time 1.69 min, column A, 2 minute gradient.
Reaction SMILES: Br[CH:2]([CH3:16])[C:3]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11](=[O:13])[N:10]([CH3:14])[C:9]=2[CH:15]=1)=O.[NH2:17][C:18]1[C:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:22][CH:21]=[CH:20][N:19]=1>>[CH2:25]([O:24][C:23]1[C:18]2[N:19]([C:2]([CH3:16])=[C:3]([C:5]3[CH:6]=[CH:7][C:8]4[O:12][C:11](=[O:13])[N:10]([CH3:14])[C:9]=4[CH:15]=3)[N:17]=2)[CH:20]=[CH:21][CH:22]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: Nc1ncccc1OCc1ccccc1
Reactant: CC(Br)C(=O)c1ccc2oc(=O)n(C)c2c1
Product: Cc1c(-c2ccc3oc(=O)n(C)c3c2)nc2c(OCc3ccccc3)cccn12
Yield: 54.5 %

Procedure:
5-(8-Benzyloxy-3-methylimidazo[1,2-a]pyridin-2-yl)-3-methyl-2-benzoxazolinone (2.1 g) was prepared in substantially the same manner as that of Example 30 from 5-(2-bromopropionyl)-3-methyl-2-benzoxazolinone (2.84 g) and 2-amino-3-benzyloxypyridine (4.8 g). mp. 210° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12](=[O:14])[CH3:13])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C1C(=O)N([Br:22])C(=O)C1>C(Cl)(Cl)(Cl)Cl>[Br:22][C:8]1[C:3]([O:2][CH3:1])=[CH:4][C:5]([NH:11][C:12](=[O:14])[CH3:13])=[CH:6][C:7]=1[O:9][CH3:10]
Reactant: COc1cc(NC(C)=O)cc(OC)c1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: COc1cc(NC(C)=O)cc(OC)c1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 25.4 %

Procedure:
N-(3,5-Dimethoxyphenyl)acetamide (500 mg, 2.56 mmol) was suspended in CCl4 (3 mL) followed by the addition of NBS (456 mg, 2.56 mmol) at room temperature. The reaction mixture was stirred at room temperature for 0.5 hour, heated at 80° C. for 2 hours and then concentrated under reduced pressure. The crude material was purified by silica gel chromatography (80 g ISCO column, eluting with 0% to 20% EtOAc in CH2Cl2) to provide Intermediate 9A (178 mg, 0.649 mmol, 25.4% yield) as a white solid. MS (ES): m/z=276.0 [M+H]+. 1H NMR (400 MHz, MeOD) δ ppm 2.14 (s, 3 H) 3.85 (s, 6 H) 7.01 (s, 2 H).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[CH:28]=[C:29](/[C:33](/[CH2:37][CH3:38])=[CH:34]/[CH:35]=O)[CH:30]=[CH:31][CH:32]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:58](Br)(Br)([Br:60])[Br:59]>[Zn]>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[CH:28]=[C:29](/[C:33](/[CH2:37][CH3:38])=[CH:34]/[CH:35]=[C:58]([Br:60])[Br:59])[CH:30]=[CH:31][CH:32]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:22])[CH3:23])([CH3:19])[CH3:20])([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]
Reactant: BrC(Br)(Br)Br
Reactant: CC/C(=C\C=O)c1cccc(CCc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)c1
Agent: [Zn]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC/C(=C\C=C(Br)Br)c1cccc(CCc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)c1

Procedure:
In a manner analogous to example 2g, by reaction of 9 g (16.3 mmol) of (E)-3-(3-{2-[3,4-bis(tert-butyldimethylsilanyloxymethyl)-phenyl]ethyl}phenyl)pent-2-enal (prepared in example 1j) with 2.1 g (32.5 mmol) of zinc powder, 8.5 g (32.5 mmol) of triphenylphosphine and 108 g (32.5 mmol) of carbon tetrabromide. A yellow oil is obtained (m=11.3 g; Y=98%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH:9]=[O:10])=[C:4]([Cl:11])[N:3]=1.[CH2:12]([NH2:17])[CH2:13][CH2:14][CH2:15][CH3:16]>CO>[NH2:1][C:2]1[N:3]=[C:4]([Cl:11])[C:5]([CH:9]=[O:10])=[C:6]([NH:17][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[N:7]=1
Reactant: Nc1nc(Cl)c(C=O)c(Cl)n1
Reactant: CCCCCN
Solvent: CO
Product: CCCCCNc1nc(N)nc(Cl)c1C=O

Procedure:
To 2-amino-4,6-dichloropyrimidine-5-carbaldehyde (30 g) in MeOH (600 ml) and TEA (22 ml), pentylamine (18.5 ml) was added and heated at reflux for 3 h. The solvent was removed and the residue partitioned between EtOAc and water, the organic layer was dried and the solvent evaporated. The residue was triturated with ether/isohexane to give the subtitle compound as a solid, 20.2 g.
Reaction SMILES: [N:1]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19][C@H:2]1[C:3]([N:5]([CH3:18])[C@H:6]([C:14]([O:16]C)=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].[OH-].[Na+]>>[N:1]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][CH2:19][C@H:2]1[C:3]([N:5]([CH3:18])[C@H:6]([C:14]([OH:16])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4]
Reactant: COC(=O)[C@H](Cc1ccccc1)N(C)C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Product: CN(C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)[C@@H](Cc1ccccc1)C(=O)O
Yield: 83 %

Procedure:
Condensation of BocProOH (4.30 g.) and HMePheOMe (2.74 g.) by the mixed anhydride method using diphenylphosphinyl chloride gave BocPro-MePheOMe in 77% yield. Demethylation of BocPro-MePheOMe (3.0 g.) using aqueous sodium hydroxide gave BocPro-MePheOH in 83% yield. Condensation of BocPro-MePheOH (1.71 g.) and HPheOBz (2.14 g.) using dicyclohexylcarbodiimide and N-hydroxysuccinimide gave BocPro-MePhe-PheOBz in 76% yield. Debenzylation of BocPro-MePhe-PheOBz (2.0 g.) by hydrogenation with palladium catalyst gave BocPro-MePhe-PheOH in 100% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:23])([CH3:22])[C:10](=[O:21])[C:11]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)=[CH:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1.[BH4-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:22])([CH3:23])[CH:10]([OH:21])[C:11]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)=[CH:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1
Reactant: CCCC=C(C(=O)C(C)(C)Cc1ccc(Cl)cc1)n1cncn1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCCC=C(C(O)C(C)(C)Cc1ccc(Cl)cc1)n1cncn1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 92.7 %

Procedure:
7 g (0.021 mol) of 1-(4-chlorophenyl)-2,2-dimethyl-4-(1,2,4-triazol-1-yl)-4-octen-3-one (Example 1) are dissolved in 100 ml of methanol, and a solution of 0.21 g (0.006 mol) of sodium borohydride in 5 ml of icewater is added dropwise at -10° C. The reaction mixture is subsequently stirred at 0° C. for 1.5 hours and is then adjusted to a pH value of 6 to 7 with dilute hydrochloric acid. The reaction mixture is concentrated by distilling off the solvent in vacuo. The residue is taken up in chloroform and the mixture is washed with water, dried over sodium sulphate and concentrated. 6.5 g (92.9% of theory) of 1-(4-chlorophenyl)-2,2-dimethyl-4-(1,2,4-triazol-1-yl)-4-octen-3-ol of refractive index nD20 1.5383 are obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:15](/[CH:16]=[CH:17]/[C:18]([O:20][CH3:21])=[O:19])=[C:14]3[N:9]([CH2:10][CH2:11][C:12]4[CH:25]=[CH:24][CH:23]=[CH:22][C:13]=43)[C:8](=[O:26])[C:7]=2[CH:27]=1>C(O)(=O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:15]([CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[C:14]3[N:9]([CH2:10][CH2:11][C:12]4[CH:25]=[CH:24][CH:23]=[CH:22][C:13]=43)[C:8](=[O:26])[C:7]=2[CH:27]=1
Reactant: COC(=O)/C=C/c1c2n(c(=O)c3cc(OC)ccc13)CCc1ccccc1-2
Agent: [Pd]
Solvent: CC(=O)O
Product: COC(=O)CCc1c2n(c(=O)c3cc(OC)ccc13)CCc1ccccc1-2
Reaction time: 3 h

Procedure:
To a solution of 3.5 g (9.68 mmol) of methyl (E)-3-(10-methoxy-8-oxo-5,8-dihydro-6H-dibenzo[a,g]quinolizin-13-yl)prop-2-enoate in 100 ml of acetic acid is added 0.5 g of 5% palladium on charcoal and the suspension is subjected to hydrogenation in a Parr apparatus at a pressure of about 0.32 MPa between 50° and 60° C. for 3 h.
Reaction SMILES: C([O:8][C:9]1[CH:38]=[CH:37][C:12]2[NH:13][C:14]([C:19]3[C:24](=[O:25])[N:23]([NH:26][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)[C:22]4[CH:33]=[CH:34][S:35][C:21]=4[C:20]=3[OH:36])=[N:15][S:16](=[O:18])(=[O:17])[C:11]=2[CH:10]=1)C1C=CC=CC=1.I[Si](C)(C)C>C(#N)C.O>[CH:27]1([NH:26][N:23]2[C:24](=[O:25])[C:19]([C:14]3[NH:13][C:12]4[CH:37]=[CH:38][C:9]([OH:8])=[CH:10][C:11]=4[S:16](=[O:18])(=[O:17])[N:15]=3)=[C:20]([OH:36])[C:21]3[S:35][CH:34]=[CH:33][C:22]2=3)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1
Reactant: O=c1c(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)c(O)c2sccc2n1NC1CCCCC1
Agent: C[Si](C)(C)I
Solvent: CC#N
Solvent: O
Product: O=c1c(C2=NS(=O)(=O)c3cc(O)ccc3N2)c(O)c2sccc2n1NC1CCCCC1
Temperature: 25 °C
Yield: 85.8 %

Procedure:
The product of Example 324D (0.114 g, 0.21 mmol) in dry acetonitrile (11 mL) at 25° C. was reacted with iodotrimethylsilane (0.29 mL, 2.1 mmol) at 50° C. for 4 hours. The reaction was cooled to 25° C. and diluted with water (50 mL). The resulting precipitate was collected by filtration and dried under reduced pressure to give the title compound (0.083 g, 87% yield). MS (ESI−) m/z 459 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.20 (m, 5 H) 1.66 (m, 5 H) 6.51 (s, 1 H) 7.18 (m, 2 H) 7.48 (d, J=5.52 Hz, 1 H) 7.57 (d, J=9.56 Hz, 1 H) 8.29 (d, J=5.15 Hz, 1 H) 10.42 (s, 1 H) 14.04 (s, 1 H) 14.93 (s, 1 H).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])=O.[F:13][C:14]1[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=1[NH2:16].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.O>[F:13][C:14]1[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=1[NH:16][CH2:1][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1cccc(C=O)c1
Reactant: Nc1ccccc1F
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: ClCCl
Product: COC(=O)c1cccc(CNc2ccccc2F)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 99.4 %

Procedure:
To a stirred solution of methyl 3-formylbenzoate (1 g, 6.092 mmol) in anhydrous DCM (30 mL) was added 2-fluoroaniline (0.620 mL, 6.396 mmol) followed by glacial acetic acid (0.350 mL, 6.092 mmol). The reaction was stirred at room temperature for 18 hours. Sodium triacetoxyborohydride (3.23 g, 15.23 mmol) was added, and the reaction was stirred at room temperature for 3 hours. Water was added to quench the reaction, and the mixture was diluted with DCM. The organic layer was washed with brine, passed through a hydrophobic fit and the solvent was removed in vacuo to afford the title compound as a yellow oil (1.57 g, quantitative yield).