Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=CC(C[NH:8][C:9]2[S:10][C:11]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([N:21]4[CH2:26][CH2:25][O:24][CH2:23][CH2:22]4)[N:16]=3)=[C:12]([CH3:14])[N:13]=2)=CC=1>FC(F)(F)C(O)=O.O>[CH3:14][C:12]1[N:13]=[C:9]([NH2:8])[S:10][C:11]=1[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:16]=1
Reactant: COc1ccc(CNc2nc(C)c(-c3ccnc(N4CCOCC4)n3)s2)cc1
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: Cc1nc(N)sc1-c1ccnc(N2CCOCC2)n1
Temperature: 75 °C

Procedure:
A solution comprising (4-methoxy-benzyl)-[4-methyl-5-(2-morpholin-4-yl-pyrimidin-4-yl)-thiazol-2-yl]-amine (25c) (0.45 g, 1.13 mmol) in trifluoroacetic acid:water (95:5) (10 ml) is heated at 75° C. for days. The solvent is removed in vacuo and the crude residue is dissolved in ethyl acetate. The pH is adjusted to pH12 using 2N sodium hydroxide and the layers are separated. The aqueous layer is extracted with ethyl acetate (2×30 ml). The organic portions are combined and washed with brine (50 ml), dried over MgSO4 and concentrated in vacuo to yield the titled compound as a brown solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:9][C@@H:10]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:11]([NH:13][CH2:14][C:15]#[N:16])=[O:12])=[N:6][CH:7]=1.CC[O:29]C(C)=O.CCCCCC>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[O:9][C@@H:10]([CH2:17][CH:18]([CH3:19])[CH3:20])[C:11]([NH:13][CH2:14][C:15]#[N:16])=[O:12])=[N+:6]([O-:29])[CH:7]=1
Reactant: CC(C)C[C@H](OC(c1ccccc1)c1ccc(Br)cn1)C(=O)NCC#N
Reactant: CCOC(C)=O
Solvent: CCCCCC
Product: CC(C)C[C@H](OC(c1ccccc1)c1ccc(Br)c[n+]1[O-])C(=O)NCC#N

Procedure:
Using the same procedure as described for example 40, (2S)-2-[(5-bromopyridin-2-yl)(phenyl)methoxy]-N-(cyanomethyl)-4-methylpentanamide (51 mg, 0.123 mmol) was oxidized to give the title compound after chromatography with 50% EtOAc/hexane.
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1.C(NC(C)C)(C)C.[CH3:35][S:36](Cl)(=[O:38])=[O:37]>ClCCl>[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][S:36]([CH3:35])(=[O:38])=[O:37])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3cccc4c3OCO4)CC2)CC1
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CC(C)NC(C)C
Product: CS(=O)(=O)N[C@H]1CC[C@H](CCN2CCN(c3cccc4c3OCO4)CC2)CC1
Reaction time: 0.17 h

Procedure:
In a 5 mL round-bottomed flask, Trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine hydrochloride (Intermediate A) (25 mg, 0.068 mmol) was solved in dichloromethane (500 μl) to give a white suspension. N,N-diisopropylamine (26.3 mg, 35.6 μl, 0.204 mmol) was added. and after 10 min stirring, methanesulfonyl chloride (11.7 mg, 7.89 μl, 0.102 mmol) was added and the reaction mixture was stirred over night at room temp. The reaction was quenched with 15 mL of saturated NaHCO3 and extracted with dichloromethane (3×20 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 10 g, 0% to 15% MeOH in dichloromethane) to yield the title compound as white solid (18 mg, 64.3%), MS (ISP) m/z=410.3 [(M+H)+].
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:30]C)[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[O:27][CH2:28][CH3:29])=[N:13][C:14]=1[CH2:15][CH3:16].ClC1C=C(Cl)C=CC=1C1N=C(C)C(N[C@@H]2C3C(=CC=CC=3)C[C@@H]2O)=NC=1CC>>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH3:30])[C:12]([NH:17][C@@H:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:20][C@@H:19]2[O:27][CH2:28][CH3:29])=[N:13][C:14]=1[CH2:15][CH3:16]
Reactant: CCO[C@H]1Cc2ccccc2[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1CC
Agent: CCc1nc(N[C@@H]2c3ccccc3C[C@@H]2O)c(C)nc1-c1ccc(Cl)cc1Cl
Product: CCO[C@H]1Cc2ccccc2[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1C

Procedure:
Following the procedure for the preparation of 5-(2,4-dichlorophenyl)-N-[(1R,2S)-2-ethoxy-2,3-dihydro-1H-inden-1-yl]-3,6-diethylpyrazin-2-amine but substituting (1R,2S)-1-{[5-(2,4-dichlorophenyl)-6-ethyl-3-methylpyrazin-2-yl]amino}-2,3-dihydro-1H-inden-2-ol and making non-critical variations provided the title compound as a solid: 1H NMR (CDCl3) δ 0.76-0.82, 1.02-1.34, 1.56-1.58, 2.24, 2.62, 3.38-3.55, 3.90-3.95, 5.22, 5.50-5.54, 6.14-6.16, 6.70-6.72, 7.04-7.62; MS (ESI+) for C24H25Cl2N3O m/z 443 (M+H)+.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10]I.[P:12]([O:19]CC)([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15]>O1CCOCC1>[CH2:14]([O:13][P:12]([CH2:10][CH2:9][O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])(=[O:19])[O:16][CH2:17][CH3:18])[CH3:15]
Reactant: CCOP(OCC)OCC
Reactant: COCCOCCOCCI
Solvent: C1COCCO1
Product: CCOP(=O)(CCOCCOCCOC)OCC

Procedure:
{2-[2-(2-Methoxyethoxy)ethoxy]ethyl}iodide (6.64 g, 24.3 mmol) and P(OEt)3 (4.22 ml, 24.3 mmol) were dissolved in 1,4-dioxane (30 ml) and stirred under reflux for 24 hours. Volatiles were distilled in vacuo (150° C., 0.01 torr) to give the crude material as a thick yellow oil. Column chromatography (silica gel, EtOAc:MeOH 95:5 elution) afforded the desired product as a pale yellow oil. Yield 1.0 g, 15%. Alternative synthesis using {2-[2-(2-Methoxyethoxy)ethoxy]ethyl}iodide (5.00 g, 18.2 mmol) and P(OEt)3 (10 ml, excess) under microwave irradiation (100 W, 1 hr) gave higher yield after column chromatography (3.06 g, 10.7 mmol, 59%). 1H NMR (CDCl3, 400 MHz, 298 K): δ 4.08 (m, 4H), 3.67 (d of t, JH-P=10 Hz, JH-H=7 Hz, 2H), 3.60 (m, 6H), 3.50 (m, 2H), 3.36 (s, 3H), 2.09 (d of t, JH-P=20 Hz, JH-H=7 Hz, 2H), 1.28 (t, J=7 Hz). 13C {1H} NMR (CDCl3, 100 MHz, 298 K): δ 71.72, 70.35, 70.30, 69.97, 64.92, 61.44 (d, JC-P=6 Hz), 58.82, 26.77 (d, JC-P=138 Hz), 16.22 (d, JC-P=6 Hz). 31P{1H} NMR (CDCl3, 162 MHz, 298 K): δ 29.23. MS (FAB, m/z): 285 ([M+H]+, 100%). Exact mass found (calculated for [M+H]+, m/z): 285.15395 (285.14670).
Reaction SMILES: [NH2:1][C@H:2]([C:9]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([I:19])=[CH:15][CH:14]=1)=[O:10])[CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6].[CH3:20][C:21]([O:24][C:25]([NH:27][C@H:28]([C:35](O)=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])([CH3:23])[CH3:22].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:21]([O:24][C:25]([NH:27][C@H:28]([C:35]([NH:1][C@@H:2]([CH2:3][CH2:4][C:5]([O:7][CH3:8])=[O:6])[C:9]([NH:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([I:19])=[CH:17][CH:18]=1)=[O:10])=[O:36])[CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:26])([CH3:22])([CH3:20])[CH3:23]
Reactant: COC(=O)CC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: COC(=O)CC[C@H](N)C(=O)NCc1ccc(I)cc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC(=O)CC[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CCC(=O)OC)C(=O)NCc1ccc(I)cc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 77.7 %

Procedure:
A solution of (S)-methyl 4-(tert-butoxycarbonylamino)-5-(4-iodobenzylamino)-5-oxopentanoate (2.129 g, 4.47 mmol) in DCM (15 mL) and TFA (10 mL) was stirred at room temperature for 4 h. After the solvent was evaporated, the reaction mixture was diluted with DCM, washed with sat. K2CO3 aqueous solution and concentrated in vacuo to afford (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g). A solution of (S)-methyl 4-amino-5-(4-iodobenzylamino)-5-oxopentanoate (1.67 g), Boc-Glu(OMe)—OH.DCHA (1.97 g, 4.44 mmol), EDCI (1.02 g, 5.33 mmol), HOBt (0.599 g, 4.44 mmol) in DCM (100 mL) containing DIPEA (2.26 mL) was stirred at room temperature under nitrogen for 20 h. The reaction mixture was diluted with DCM, washed with 1N HCl aqueous solution, sat. NaHCO3 aqueous solution and brine. The organic phase was separated and evaporated under reduced pressure to give a crude product, which was purified by flash chromatography with hexane/ethyl acetate as eluent to give (S)-methyl 4-(tert-butoxycarbonylamino)-5-((S)-1-(4-iodobenzylamino)-5-methoxy-1,5-dioxopentan-2-ylamino)-5-oxopentanoate (2.137 g, 77% over 2 steps) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.62 (d, J=8.4 Hz, 2H), 7.20 (s, 1H), 7.00 (d, J=8.4 Hz, 2H), 5.44 (brs, 1H), 4.48-4.30 (m, 3H), 4.06-4.02 (m, 1H), 3.69 (s, 6H), 2.54-2.37 (m, 4H), 2.20-1.93 (m, 3H), 1.37 (s, 9H); MS (ESI), 620 (M+H)+.
Reaction SMILES: [CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([CH:23]=O)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2].[NH2:25][C:26]1[CH:30]=[CH:29][O:28][N:27]=1>>[CH:1]([N:4]1[C:8]([C:9]2[S:10][C:11]3[CH2:12][CH2:13][O:14][C:15]4[CH:22]=[C:21]([CH2:23][NH:25][C:26]5[CH:30]=[CH:29][O:28][N:27]=5)[CH:20]=[CH:19][C:16]=4[C:17]=3[N:18]=2)=[N:7][CH:6]=[N:5]1)([CH3:3])[CH3:2]
Reactant: Nc1ccon1
Reactant: CC(C)n1ncnc1-c1nc2c(s1)CCOc1cc(C=O)ccc1-2
Product: CC(C)n1ncnc1-c1nc2c(s1)CCOc1cc(CNc3ccon3)ccc1-2
Yield: 52 %

Procedure:
Following the procedure for 119, 2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-8-carbaldehyde and 3-amino-isoxazole were reacted. Purification by flash chromatography (SiO2, 0-20% EtOAc in DCM) gave 284 as a white solid (154 mg, 52%). LCMS: RT=10.79 min, [M+H]+=409. 1H NMR δ (ppm) (CDCl3): 8.33 (1H, d, J=8.10 Hz), 8.04 (1H, d, J=1.68 Hz), 7.90 (1H, s), 7.16 (1H, d, J=8.19 Hz), 7.06 (1H, s), 5.93-5.84 (1H, m), 5.85-5.83 (1H, m), 4.42 (2H, s), 4.38 (2H, t, J=5.02 Hz), 3.42-3.36 (2H, m), 1.60 (6H, d, J=6.62 Hz). 1 Exchangeable proton not seen.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[F:10][C:11]1[CH:16]=[C:15](Br)[CH:14]=[CH:13][C:12]=1[O:18][CH3:19].C([O-])([O-])=O.[K+].[K+].O>CN1CCCC1=O>[F:10][C:11]1[CH:16]=[C:15]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)[CH:14]=[CH:13][C:12]=1[O:18][CH3:19]
Reactant: c1ccc2[nH]ccc2c1
Reactant: COc1ccc(Br)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN1CCCC1=O
Product: COc1ccc(-n2ccc3ccccc32)cc1F

Procedure:
Indole (60 g, 0.51 mole), o-fluoro-p-bromoanisole (112.2 g, 0.547 mole), K2CO3 (76 g, 0.55 mole) and Cu2Br2 (14 g) were combined in 600 ml N-methylpyrrolidone and heated at 185°-200° for 48 hours, stirring under N2. The reaction mixture was cooled, poured into ice and water and extracted several times with ethyl acetate. The combined organic layers were washed with H2O, then brine, dried over MgSO4, treated with activated carbon, and concentrated to an oil (148 g). A portion of the oil (25 g) was chromatographed on silica gel (7.5×18 cm) eluting with 1:9 CH2Cl2 : hexane, yielding title product as an oil which crystallized on standing in vacuo overnight, 7.2 g, m.p. 65°-67°.
Reaction SMILES: [N:1]1O[C:3]([O-])=[C:4]2[CH2:9][CH2:8][CH2:7][CH2:6][N+:5]=12.[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]#C)=[CH:14][CH:13]=1>C1(C)C=C(C)C=C(C)C=1>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:3]=[C:4]3[CH2:9][CH2:8][CH2:7][CH2:6][N:5]3[N:1]=2)=[CH:14][CH:13]=1
Reactant: C#Cc1ccc(F)cc1
Reactant: [O-]c1on[n+]2c1CCCC2
Solvent: Cc1cc(C)cc(C)c1
Product: Fc1ccc(-c2cc3n(n2)CCCC3)cc1
Temperature: 165 °C
Reaction time: 16 h
Yield: 24.9 %

Procedure:
A mixture of 2.44 g (16.5 mmol) of 4,5,6,7-tetrahydro[1,2,3]oxadiazolo[3,4-a]pyridin-8-ium 3-olate and 2.15 g (16.5 mmol) of 4-fluorophenylacetylene in 80 ml of mesitylene is stirred under argon at 165° C. for 16 h. After cooling, the reaction mixture is concentrated under reduced pressure. Purification by column chromatography on silica gel (cyclohexane/ethyl acetate) gives 888 mg (27%) of the desired product; log P(HCOOH): 2.76; 1H-NMR (MeCN-d3): 7.76 (dd, 2H), 7.11 (dd, 2H), 6.29 (s, 1H), 4.09 (dd, 2H), 2.79 (dd, 2H), 2.02 (m, 2H), 1.84 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[C:6]([Cl:9])[C:7]=1F.[CH:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH:17]=1)=[CH2:15].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[N:18]1[C:19]2[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:16]([C:14]#[CH:15])=[CH:17]1
Reactant: Fc1c(Cl)cc(C(F)(F)F)cc1Cl
Reactant: C=Cc1c[nH]c2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C#Cc1cn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c2ccccc12
Temperature: 90 °C
Reaction time: 8 h
Yield: 18.1 %

Procedure:
To a solution of 3,5-dichloro-4-fluorobenzotrifluoride (4.79 g) in dimethylformamide (25 ml) was added 3-ethenylindole (2.9 g) and potassium carbonate (2.84 g), the mixture was heated at 90° C. for 3 hours under an atmosphere of nitrogen and then left to stir overnight at room temperature. The reaction was diluted with water (100 ml) and extracted with hexane (2×100ml). The organic fractions were separated, combined, evaporated to dryness and purified by column chromatography on silica gel (300 g) eluted with hexane:ethylacetate (97:3) to give the title compound as a white solid (1.3 g), m.p. 120-122 ° C.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][NH:12][CH3:13])=[CH:8][C:6]=2[N:7]=1.[C:20](Cl)(=[O:22])[CH3:21].C(N(CC)CC)C>ClCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]2[S:10][C:9]([CH2:11][N:12]([CH3:13])[C:20](=[O:22])[CH3:21])=[CH:8][C:6]=2[N:7]=1
Reactant: CNCc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N(C)Cc1cc2nc(Cl)nc(N3CCOCC3)c2s1
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a solution of (2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-methylamine (120 mg) in dichloromethane (2 ml) was added acetyl chloride (31.4 μL) and triethylamine (61.6 μL). The reaction mixture was stirred at room temperature for 3.5 hours, then diluted with dichloromethane, washed with brine, dried (MgSO4) and the solvents removed in vacuo to give a crude residue. This was purified by flash chromatography to yield N-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-N-methyl-acetamide (110 mg).
Reaction SMILES: [I:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[Si:33]([O:40][CH2:41][C@H:42]([NH2:50])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[I:49])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>C1COCC1.C(N(CC)CC)C>[Si:33]([O:40][CH2:41][C@H:42]([NH:50][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=1[I:1])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[I:49])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H](N)c1ccccc1I
Reactant: O=C(O)c1ccccc1I
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OC[C@H](NC(=O)c1ccccc1I)c1ccccc1I
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 2-iodobenzoic acid (0.66 g, 2.65 mmol) in THF (90 mL) is added HOBt (0.71 g, 5.3 mmol). After the mixture is stirred at RT for 15 min, EDCl (1.0 g, 5.3 mmol) is added followed by triethylamine (1.1 mL). The mixture is stirred at RT for 20 min then (R)-2-(tert-butyldimethylsilanyloxy)-1-(2-iodophenyl)-ethylamine (Org. Lett. 6, 513 (2004)) (1.0 g, 2.65 mmol) is added and stirring is continued for 18 h. The solvent is removed under reduced pressure and water is added to the residue. The mixture is extracted with EtOAc and the organic phase is washed with brine and dried over magnesium sulfate. The solvent is removed under reduced pressure and the residue purified by flash chromatography using a gradient of 0-60% EtOAc/hexane as eluent to give the title compound as a yellow solid.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:30]=[CH:29][C:13]3[N:14]4[CH:19]=[C:18]([C:20]5[CH:25]=[CH:24][C:23]([N+:26]([O-])=O)=[CH:22][CH:21]=5)[N:17]=[C:15]4[S:16][C:12]=3[CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CO.[H][H]>[Ni].C1COCC1>[N:1]1([CH2:7][CH2:8][O:9][C:10]2[CH:30]=[CH:29][C:13]3[N:14]4[CH:19]=[C:18]([C:20]5[CH:21]=[CH:22][C:23]([NH2:26])=[CH:24][CH:25]=5)[N:17]=[C:15]4[S:16][C:12]=3[CH:11]=2)[CH2:2][CH2:3][O:4][CH2:5][CH2:6]1
Reactant: O=[N+]([O-])c1ccc(-c2cn3c(n2)sc2cc(OCCN4CCOCC4)ccc23)cc1
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Solvent: C1CCOC1
Product: Nc1ccc(-c2cn3c(n2)sc2cc(OCCN4CCOCC4)ccc23)cc1

Procedure:
Intermediate 3 is dissolved into Methanol and THF and placed in a Hydrogenator. Raney Nickel is added and the vessel is pressurized with Hydrogen and stirred for >24 hrs. The reaction mixture is concentrated to a thick paste and diluted with Methyl tert-butyl ether. The resulting solids are filtered and washed with Methyl tert-butyl ether and dried under vacuum to give Intermediate 4.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8](=[O:10])[S:7][C:6]=2[CH:11]=1.[CH2:12]([C:14]1[CH:15]=[C:16]([N:20]=[C:21]=[O:22])[CH:17]=[CH:18][CH:19]=1)[CH3:13].C(N(CC)CC)C>C(C(C)=O)C>[CH2:12]([C:14]1[CH:15]=[C:16]([NH:20][C:21]([O:1][C:2]2[CH:3]=[CH:4][C:5]3[O:9][C:8](=[O:10])[S:7][C:6]=3[CH:11]=2)=[O:22])[CH:17]=[CH:18][CH:19]=1)[CH3:13]
Reactant: O=c1oc2ccc(O)cc2s1
Reactant: CCc1cccc(N=C=O)c1
Solvent: CCN(CC)CC
Solvent: CCC(C)=O
Product: CCc1cccc(NC(=O)Oc2ccc3oc(=O)sc3c2)c1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
5-hydroxy-1,3-benzoxathiol-2-one (15.0 grams) was mixed with 3-ethylphenyl isocyanate (13.1 grams) in 180 milliliters of methyl ethyl ketone in the presence of 0.90 gram of triethylamine. This solution was heated at reflux temperature with stirring for 3 hours and 15 minutes. The solvent was then removed by evaporation in vacuo and the residual, viscous oil was dissolved in a hot mixture of ethyl acetate and methylcyclohexane. Upon slowly cooling to room temperature, the solution gave the purified 5-[(3-ethylphenyl)carbamoyloxy]-1,3-benzoxathiol-2-one as a white crystalline solid with a melting point of 96°-97° C. Elemental analysis calculated for C16H13NO4S (percent): carbon--60.94; hydrogen--4.15; nitrogen--4.44. Found: carbon--61.2; hydrogen--4.26; nitrogen--4.54.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]([CH:16]([C:18](C)=[O:19])[CH3:17])[C:10]1=[O:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[OH:23].[OH-].[Na+]>O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]([CH:16]([C:18]([OH:19])=[O:23])[CH3:17])[C:10]1=[O:21])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)C(C)N1CCCC[C@H](NC(=O)OC(C)(C)C)C1=O
Reactant: CO
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C(=O)O)N1CCCC[C@H](NC(=O)OC(C)(C)C)C1=O
Reaction time: 2 h

Procedure:
Dissolve 2.59 g 3-(S)-t-butoxycarbonylamino-1-(1-methylcarbonylethyl)perhydroazepin-2-one in 10 ml. methanol and 10 ml water and add 0.5 ml 50% NaOH solution. Store the mixture at room temperature for 2 hours and then concentrate at aspirator pressure to a syrup. Dissolve the syrup in water and chill the solution in an ice bath. Add 6N hydrochloric acid to pH 2 then extract the solution several times with ethyl acetate. Dry the combined extracts over MgSO4, filter and concentrate the filtrate at aspirator pressure and isolate 3-(S)-t-butoxycarbonylamino-1-(1-carboxyethyl)perhydroazepin-2-one as an oil (2.04 g) which is a mixture of diastereomers. Separate the isomers on a column of XAD2 resin at 50° C. using 0.1N NH4OH containing 6% acetonitrile as eluent. Isolate the ammonium salt of the desired isomer as the one which elutes first (u.v. and refractive index detection).
Reaction SMILES: N[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5](SC2C=CC(S(O)(=O)=O)=CC=2)=[CH:4][C:3]=1OC1C=CC(S(O)(=O)=O)=C(N)C=1.NC1C=C(S(O)(=O)=O)C=CC=1>>[CH:9]1[C:8]2[C:7](=[O:17])[C:6]3[C:15](=[CH:2][CH:3]=[CH:4][CH:5]=3)[C:14](=[O:16])[C:13]=2[CH:12]=[CH:11][CH:10]=1
Reactant: Nc1cc(Oc2cc(Sc3ccc(S(=O)(=O)O)cc3)c3c(c2N)C(=O)c2ccccc2C3=O)ccc1S(=O)(=O)O
Agent: Nc1cccc(S(=O)(=O)O)c1
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
Example 3 was repeated, provided that the compounds shown in 1st, 2nd and 3rd columns of the following table were used in place of the 1-amino-2-(3'-amino-4'-sulfophenoxy)-4-(4'-sulfophenylthio)anthraquinone, 1-aminobenzene-4-β-sulfatoethylsulfone and 3-aminobenzenesulfonic acid respectively, thereby obtaining a corresponding anthraquinone. The color shade obtained by dyeing cotton with the anthraquinone compound is as shown in a 4th column of the table. Each compound can exhibit superior dye performances as described hereinabove.
Reaction SMILES: [S:1]([O:8]S(C(F)(F)F)(=O)=O)([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2].[CH2:16]([C:23]1[NH:24][C:25](=O)[C:26]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:29][CH2:28][C:27]=2[N:40]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N1C=CC=CC=1>C(Cl)Cl>[CH2:16]([C:23]1[N:24]=[C:25]([O:8][S:1]([C:4]([F:7])([F:6])[F:5])(=[O:3])=[O:2])[C:26]2[CH2:32][CH2:31][N:30]([C:33]([O:35][C:36]([CH3:38])([CH3:37])[CH3:39])=[O:34])[CH2:29][CH2:28][C:27]=2[N:40]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCc2nc(Cc3ccccc3)[nH]c(=O)c2CC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N1CCc2nc(Cc3ccccc3)nc(OS(=O)(=O)C(F)(F)F)c2CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
Triflic anhydride (516 mg, 0.30 mL, 1.83 mmol) was added dropwise to a solution of the product of Step A (500 mg, 1.41 mmol) and pyridine (167 mg, 0.17 mL, 2.11 mmol) in CH2Cl2 (5.0 mL) at 0° C. The resulting solution was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was quenched by addition of water then partitioned between 5% citric acid and ethyl acetate. The organic layer was washed with sodium bicarbonate (sat.), dried over magnesium sulfate and concentrated under vacuum to yield the crude product as a yellow gum (670 mg). This material was taken on without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[CH2:6][N:7]3[CH:14]=[C:13]([CH3:15])[CH:12]=[C:8]3[C:9](=O)[NH:10][C:4]=2[CH:3]=1.P(Cl)(Cl)([Cl:20])=O.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+]>ClC1C=CC=CC=1>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]2[CH2:6][N:7]3[CH:14]=[C:13]([CH3:15])[CH:12]=[C:8]3[C:9]([Cl:20])=[N:10][C:4]=2[CH:3]=1
Reactant: Cc1cc2n(c1)Cc1ccc(Cl)cc1NC2=O
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: Clc1ccccc1
Product: Cc1cc2n(c1)Cc1ccc(Cl)cc1N=C2Cl
Temperature: 25 °C

Procedure:
To a suspension of 1.1 g of 8-chloro-2-methyl-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-11-one in 20 mL of chlorobenzene is added 680 mg of phosphorous oxychloride. The mixture is heated at 100°-110° for 1 hour, then allowed to cool to room temperature. Methylene chloride (150 mL) is added to the stirred reaction mixture which is then poured into a mixture of ice and aqueous sodium carbonate. After being shaken vigorously, the methylene chloride layer is separated, the aqueous layer is further extracted with 200 ml of diethyl ether; the combined extracts are dried (anhydrous magnesium sulfate), decolorized with charcoal, and evaporated to dryness to yield 8,11-dichloro-2-methyl-5H-pyrrolo[2,1-c][1,4]benzodiazepine as a viscous oil which is used in the next step without further purification.