Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+](C1C=CC(COC([NH:12][C@H:13]2[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]3[CH2:24][C@H:23]([S:25][C:26]4[C@H:27]([CH3:50])[C@@H:28]5[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]5[C:30]=4[C:31]([O:33]CC4C=CC([N+]([O-])=O)=CC=4)=[O:32])[CH2:22][N:21]3[CH3:51])=[O:19])[CH2:14]2)=O)=CC=1)([O-])=O.[ClH:54]>O1CCCC1.O>[ClH:54].[NH2:12][C@H:13]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:24][C@H:23]([S:25][C:26]3[C@H:27]([CH3:50])[C@@H:28]4[C@@H:45]([C@H:46]([OH:48])[CH3:47])[C:44](=[O:49])[N:29]4[C:30]=3[C:31]([OH:33])=[O:32])[CH2:22][N:21]2[CH3:51])=[O:19])[CH2:14]1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](NC(=O)OCc5ccc([N+](=O)[O-])cc5)C4)N(C)C3)[C@H](C)[C@H]12
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(S[C@H]3C[C@@H](C(=O)N4CC[C@H](N)C4)N(C)C3)[C@H](C)[C@H]12

Procedure:
1.0 g of 4-nitrobenzyl (1R, 5S, 6S)-2-{(2S, 4S)-2-[(3S)-3-(4-nitrobenzyloxycarbonyl)aminopyrrolidin-1-ylcarbonyl]-1-methylpyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate [prepared as described in step (a) above] was dissolved in 30 ml of a 2:1 by volume mixture of tetrahydrofuran and water, after which 1.04 ml of 1N aqueous hydrochloric acid was added, and the mixture was hydrogenated by bubbling hydrogen through it at room temperature for 2 hours in the presence of 1.5 g of 10% w/w palladium-on-charcoal. At the end of this time, the reaction mixture was worked up and purified by the same procedure as described in Example 18(b), to give 175 mg of the title compound as a powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]([NH:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].[CH2:36](Br)[CH2:37][CH3:38]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][C:33]=1[O:34][CH3:35])[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:36][CH2:37][CH3:38])=[C:14]([O:17][CH3:18])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH2:20][C:21]([NH:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22]
Reactant: CCCBr
Reactant: COc1cc2c(cc1O)CCN(CC(=O)NCc1ccccc1)C2Cc1ccc(OC)c(OC)c1
Product: CCCOc1cc2c(cc1OC)C(Cc1ccc(OC)c(OC)c1)N(CC(=O)NCc1ccccc1)CC2

Procedure:
prepared by reaction of 2-[1-(3,4-dimethoxy-benzyl)-6-hydroxy-7-methoxy-3,4-dihydro-1H-isoquinolin-2-yl]-N-benzyl-acetamide with propyl bromide
Reaction SMILES: [C:1]1([CH3:41])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=4)[N:21](S(C4C=CC(C)=CC=4)(=O)=O)[CH:20]=3)=[CH:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Li+].[OH-]>C1COCC1.CO.O>[C:1]1([CH3:41])[CH:2]=[CH:3][C:4]([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]([C:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=4)[NH:21][CH:20]=3)=[CH:11]2)(=[O:8])=[O:9])=[CH:5][CH:6]=1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cn(S(=O)(=O)c4ccc(C)cc4)c4ccc([N+](=O)[O-])cc34)c3ccccc32)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2cc(-c3c[nH]c4ccc([N+](=O)[O-])cc34)c3ccccc32)cc1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 88.6 %

Procedure:
To a solution of 223 (0.2 g, 0.34 mmol) in THF/MeOH/H2O (5:5:1) was added LiOH (0.052 g, 2.2 mmol) (Scheme 16). The reaction mixture was stirred at 50° C. for 0.5 h. The solution was cooled to room temperature and concentrated. Water (10 mL) was added and pH was adjusted to 7 with 1N HCl. The aqueous phase was extracted with ethyl acetate (3×10mL). The combined organic phase was dried with MgSO4, and the solvent was removed in vacuo. The residue was purified by flash chromatography (ethyl acetate/hexane, 1:1, V:V) to yield QR-0170 (0.13 g, 89%), 1H NMR (DMSO): 2.30 (s, 3H), 7.33-7.39 (m, 3H), 7.45 (t, 1H, J=7.6), 7.66 (d, 1H, J=9.0), 7.80 (d, 1H, J=7.8), 7.96 (d, 2H, J=8.3), 8.06-8.10 (m, 3H), 8.13 (s, 1H), 8.60 (d, 1H, J=1.7), 12.18 (s, 1H); 13C NMR (DMSO): 21.49, 109.45, 112.89, 114.04, 116.56, 116.89, 117.64, 121.21, 123.24, 124.33, 125.48, 125.78, 127.29, 128.41, 129.84, 130.71, 134.52, 135.20, 139.97, 141.60, 146.03.
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:6]([CH3:16])[N:5]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.C(N(CC)C(C)C)(C)C.CC1(C)C(C)(C)OB([C:40]2[CH:49]=[CH:48][C:43]3[NH:44][C:45](=[O:47])[NH:46][C:42]=3[CH:41]=2)O1>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:16][C:6]1[C:7]([CH:8]([CH2:13][CH2:14][CH3:15])[C:9]([O:11][CH3:12])=[O:10])=[C:2]([C:40]2[CH:49]=[CH:48][C:43]3[NH:44][C:45](=[O:47])[NH:46][C:42]=3[CH:41]=2)[N:3]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:5]=1
Reactant: CCCC(C(=O)OC)c1c(C)nc(-c2ccccc2)nc1Cl
Reactant: CC1(C)OB(c2ccc3[nH]c(=O)[nH]c3c2)OC1(C)C
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CCCC(C(=O)OC)c1c(C)nc(-c2ccccc2)nc1-c1ccc2[nH]c(=O)[nH]c2c1
Yield: 131.1 %

Procedure:
This compound was prepared according to general method E from methyl 2-(4-chloro-6-methyl-2-phenylpyrimidin-5-yl)pentanoate (0.159 g; 0.5 mmol), tetrakis(triphenylphosphine) palladium(0) (0.059 mg; 0.05 mmol), N,N-diisopropylethylamine (0.345 mL; 2 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2(3H)-one (0.325 g; 1.25 mmol) in DME-water (2 mL) for 30 min. Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (5-100%) in heptane furnished 0.273 g (85%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][N:3]=1.N1C=CC=CC=1.[C:15]1([O:21][C:22](Cl)=[O:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[Br:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:22](=[O:23])[O:21][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:6][CH:7]=1
Reactant: Nc1ccc(Br)nc1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: O=C(Nc1ccc(Br)nc1)Oc1ccccc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 2-bromo-5-aminopyridine (3.0 g, 17.3 mmol) in THF (44 mL) cooled to 0° C. was added pyridine (1.8 mL, 21.7 mmol) followed by phenylchloroformate (2.3 mL, 18.2 mmol). A precipitate formed and the reaction was stirred at 0° C. for 1 h. The reaction was stirred at RT overnight and quenched with 1N HCl. The mixture was extracted with EtOAc. The organic layer was washed with water, saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated to give the title compound as a biege solid (4.81 g, 94% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[C:4](O)([C:18]([F:21])([F:20])[F:19])[C:5]1[C:9](=[O:10])[N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:7][C:6]=1[CH3:17].S(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:23])[C:4](=[C:5]1[C:9](=[O:10])[N:8]([C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:7]=[C:6]1[CH3:17])[C:18]([F:20])([F:21])[F:19]
Reactant: COC(=O)C(O)(c1c(C)[nH]n(-c2ccccc2)c1=O)C(F)(F)F
Solvent: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: COC(=O)C(=C1C(=O)N(c2ccccc2)N=C1C)C(F)(F)F

Procedure:
To a toluene solution (50 ml) of 2,5-dihydro-α-hydroxy-3-methyl-5-oxo-1-phenyl-α-(trifluoromethyl)-1H-pyrazole-4-acetic acid methyl ester (1.5 g, 4.5 mmol), thionyl chloride (2 ml, 22.5 mmol) was added and the mixture was stirred under reflux for 3 hours. After concentrating the liquid reaction mixture under reduced pressure, the title compound was obtained as a reddish brown solid (4.41 g).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1C(O)=O.[CH3:12][Mg]Br.CC[O:17][CH2:18][CH3:19].Cl.[OH-].[Na+]>C1COCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Br:11])=[CH:7][C:3]=1[C:18]([OH:17])([CH3:19])[CH3:12]
Reactant: CCOCC
Reactant: C[Mg]Br
Reactant: Nc1ccc(Br)cc1C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(O)c1cc(Br)ccc1N
Temperature: 25 °C
Reaction time: 48 h
Yield: 57 %

Procedure:
A solution of 2-amino-5-bromobenzoic acid (10 g, 46 mmol) in dry THF (200 mL) was treated at −78° C. under nitrogen with a solution of methylmagnesium bromide in ether (3.0 M, 90 mL, 270 mmol). The reaction mixture was slowly warmed to ambient temperature, kept stirring for 48 hours under nitrogen and then poured into a cold 0.5 N aqueous hydrochloride solution (300 mL). The mixture was neutralized with aqueous 1 N sodium hydroxide solution and ethyl acetate (300 mL) was added. The organic layer was separated and aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried (MgSO4). After removal of solvent in vacuo, the residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/3:2) to give 2-(2-amino-5-bromophenyl)propan-2-ol as off-white solid (6 g, 57%): mp 62-63° C.; 1H-NMR (CDCl3) δ7.19 (d, 1H, J=2.3 Hz), 7.12 (dd, 1H, J=8.4, 2.3 Hz), 6.51 (d, 1H, J=8.4 Hz), 4.70 (s, 2H), 1.82 (s, 1H), 1.65 (s, 6H).
Reaction SMILES: [CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[CH2:7][CH:8]1[C:20](=[O:21])[N:12]2[C:13]3[C:18]([CH:19]=[C:11]2[CH2:10][CH2:9]1)=[CH:17][CH:16]=[CH:15][CH:14]=3.[H-].[Na+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C)C=O.O>[CH2:24]([N:6]1[C:2]([CH3:1])=[C:3]([CH2:7][CH:8]2[C:20](=[O:21])[N:12]3[C:13]4[C:18]([CH:19]=[C:11]3[CH2:10][CH2:9]2)=[CH:17][CH:16]=[CH:15][CH:14]=4)[N:4]=[CH:5]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: ClCc1ccccc1
Reactant: Cc1[nH]cnc1CC1CCc2cc3ccccc3n2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c(CC2CCc3cc4ccccc4n3C2=O)ncn1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 70.8 %

Procedure:
To a suspension of 8,9-dihydro-7-[(5-methyl-1H-imidazol-4-yl)methyl]pyrido[1,2-a]indol-6(7H)-one (500 mg) in N,N-dimethylformamide (5 ml) at room temperature was added sodium hydride (60% in mineral oil, 79 mg). After stirring at room temperature for 10 minutes and then at 5° C. for 5 minutes, the solution was treated with a solution of benzyl chloride (249 mg) in N,N-dimethylformamide (1 ml) at 5° C. The mixture was stirred at 5° C. for 10 minutes and then at room temperature for 2 hours. The reaction mixture was diluted with chilled water and extracted twice with chloroform. The chloroform layer was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The oil obtained was purified by silica gel column chromatography (1% methanol-chloroform) to give 7-[(1-benzyl-5-methyl-1H-imidazol-4-yl)methyl]-8,9-dihydropyrido[1,2-a]indol-6(7H)-one (468 mg).
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][NH:5][CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.[CH3:18][O:19][C:20](=[O:23])[CH2:21]Cl>CCOC(C)=O>[CH3:18][O:19][C:20](=[O:23])[CH2:21][N:4]1[CH:3]=[C:2]([I:1])[CH:6]=[N:5]1
Reactant: COC(=O)CCl
Reactant: Ic1cn[nH]c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)Cn1cc(I)cn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of 4-iodopyrazole (1.000 g, 5.155 mmol), Cs2CO3 (2.016 g, 6.186 mmol) and DMF (20 mL, 0.2 mol) was added chloroacetic acid methyl ester (0.5440 mL, 6.186 mol) at 0° C. The reaction was allowed to stir for 1 h at rt. The material was transferred to a separatory funnel, diluted with EtOAc, and washed with water several times to remove DMF. The organic layer was dry-loaded onto silica gel, and column chromatography was used to purify, eluting with 3:1 Hexanes/EtOAc, affording the title compound as a clear liquid. 1H NMR (400 MHz, CDCl3): δ=3.79 (s, 3H), 4.93 (s, 2H), 7.54 (s, 1H), 7.57 (s, 1H). MS (ES+): m/z=266.95 (100) [MH+]. HPLC: tR=2.73 min (ZQ3, polar—5 min).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3[CH:23]=[CH:22][C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][CH:14]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].O1CCCC1.Cl>O.C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3[CH:23]=[CH:22][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(-c3ccc(Cl)cc3)s2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)c1ccc(-c2ccc(-c3ccc(Cl)cc3)s2)cc1
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 59.8 %

Procedure:
A mixture of ethyl 4-[5-(4-chlorophenyl)-2-thienyl]benzoate (1.03 g), 1 M aqueous sodium hydroxide solution (4.5 ml), tetrahydrofuran (30 ml) and ethanol (30 ml) was stirred at 60° C. for 1.5 hrs. After cooling, the reaction mixture was poured into water, and 1 M hydrochloric acid (15 ml) was added. The crystals were collected by filtration and recrystallized from ethanol to give 4-[5-(4-chlorophenyl)-2-thienyl]benzoic acid (0.566 g, yield 60%) as a pale-green crystalline powder. melting point: 285–286° C.
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][N:13]([CH:20]2[CH2:22][CH:21]2[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:8][CH2:7]1)#[N:2].[N-:29]=[N+:30]=[N-:31].[Na+].[Cl-].[NH4+]>CN(C)C=O>[NH:29]1[C:1]([CH2:3][CH2:4][CH2:5][N:6]2[CH2:11][CH2:10][CH:9]([CH2:12][N:13]([CH:20]3[CH2:22][CH:21]3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16])[CH2:8][CH2:7]2)=[N:2][N:31]=[N:30]1
Reactant: [N-]=[N+]=[N-]
Reactant: N#CCCCN1CCC(CN(C(=O)C(F)(F)F)C2CC2c2ccccc2)CC1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(N(CC1CCN(CCCc2nnn[nH]2)CC1)C1CC1c1ccccc1)C(F)(F)F

Procedure:
A mixture of N-((1-(3-cyanopropyl)piperidin-4-yl)methyl)-2,2,2-trifluoro-N-(2-phenylcyclopropyl)acetamide (260 mg, 0.661 mmol), sodium azide (129 mg, 1.982 mmol), ammonium chloride (159 mg, 2.97 mmol) in N,N-dimethylformamide (DMF) (20 mL) was heated to 110° for 16 hours. Added sodium azide (129 mg, 1.982 mmol) and ammonium chloride (159 mg, 2.97 mmol) and heated to 110° for 16 hours. Concentrated and HPLC purification (reverse phase) was performed. A 7 minute gradient was run (10% AcCN/H2O, 0.1% Formic Acid to 50% ACN/H2O, 0.1% Formic Acid). Obtained 36 mg N20984-94-2(oil) [M+H]+=437.3
Reaction SMILES: CC(C)(C)C(OC[N:7]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][C:21]([CH:24]=[O:25])=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)=[N:8]1)=O.[OH-].[Na+].CC(O)=O>C1COCC1.CO>[NH:7]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[C:14]([C:18]3[CH:23]=[CH:22][C:21]([CH:24]=[O:25])=[CH:20][CH:19]=3)[CH:15]=[CH:16][CH:17]=2)=[N:8]1
Reactant: CC(C)(C)C(=O)OCn1ccc(-c2cccc(-c3ccc(C=O)cc3)c2)n1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: CC(=O)O
Product: O=Cc1ccc(-c2cccc(-c3cc[nH]n3)c2)cc1
Reaction time: 0.5 h

Procedure:
To a solution of [3-(4′-formyl-3-biphenylyl)-1H-pyrazol-1-yl]methyl 2,2-dimethyl-propanoate (0.162 g; 0.45 mmol) in 1:1 THF/MeOH (5 mL total vol) at room temperature was added NaOH (1.1 mL of a 1.0M solution; 1.1 mmol). After 30 min, HOAc (0.08 mL; 1.4 mmol) was added and the mixture was concentrated in vacuo. The residue was partitioned between EtOAc/water, layers were separated, the organic layer was washed (satd NaHCO3, brine), dried over Na2SO4 and concentrated in vacuo. The residue was redissolved in EtOAc, washed (1M HCl, water, brine), dried over Na2SO4 and concentrated in vacuo, affording the title compound as a glassy semi-solid which was used without further purification. LC/MS (method A) 2.42 min; m/z 249 (M+H).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]([NH:14][C:15](=[O:24])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:4]=1.[C:25](Cl)(=[O:31])[O:26][CH2:27][CH:28]([CH3:30])[CH3:29]>>[CH3:29][CH:28]([CH3:30])[CH2:27][O:26][C:25](=[O:31])[NH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]([NH:14][C:15](=[O:24])[CH2:16][C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:4]=1
Reactant: NCc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12
Reactant: CC(C)COC(=O)Cl
Product: CC(C)COC(=O)NCc1nn(NC(=O)Cc2ccc(Cl)cc2)c(=O)c2ccccc12

Procedure:
The product of Example 42 and 2-methylpropyl carbonochloridate were treated using a method similar to that described in Example 128 to give the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 11.59-11.61 (bs, 1H), 8.32 (dd, J=7.8, 1.4 Hz, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.96-8.02 (m, 1H), 7.88-7.94 (m, 1H), 7.65-7.75 (m, 1H), 7.36-7.45 (m, 4H), 4.50 (d, J=5.9 Hz, 2H), 3.77 (d, J=6.6 Hz, 2H), 3.67 (s, 2H), 1.73-1.89 (m, 1H), 0.67-0.68 (m, 6H); MS (ESI−) M/Z 441 (M−H)−.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C@@H:3]([OH:21])[CH2:4][C@@H:5]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:29][O:30][C:31]([NH:33][C@@H:34]([C@@H:38]([CH3:41])[CH2:39][CH3:40])[C:35](O)=[O:36])=[O:32].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:22]([C@H:2]([NH:1][C:35]([C@@H:34]([NH:33][C:31](=[O:32])[O:30][CH3:29])[C@@H:38]([CH3:41])[CH2:39][CH3:40])=[O:36])[C@@H:3]([OH:21])[CH2:4][C@@H:5]([NH:13][C:14]([O:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[O:20])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CC[C@H](C)[C@H](NC(=O)OC)C(=O)O
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@@H](N)Cc1ccccc1
Agent: CCOP(=O)(OCC)On1nnc2ccccc2c1=O
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](C)[C@H](NC(=O)OC)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of the product from Example 6A (0.50 g, 1.30 mmol) in THF (13 mL) was treated with the product from Example 5A (0.30 g, 1.59 mmol), DEPBT (0.45 g, 1.50 mmol), and N,N-diisopropylethylamine (1.1 mL, 6.31 mmol), stirred at 25° C. for 16 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 to give the title compound, used without further purification.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH2:8][C@H:9](NC(=O)OC(C)(C)C)[C:10]([N:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[CH3:13])=[O:11])[CH:5]=[CH:6][CH:7]=1.[CH2:30]([C:33]1[N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:35]2[C:40]([C:41]=1[CH2:42][C:43](O)=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=[CH2:32].CC[N:55](C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(O)(C(F)(F)F)=O.CN(C=O)C.CCOC(C)=O>[CH2:30]([C:33]1[N:34]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[C:35]2[C:40]([C:41]=1[CH2:42][C:43]([NH:55][C@@H:9]([CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([I:1])[CH:3]=1)[C:10]([N:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[CH3:13])=[O:11])=[O:44])=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:31]=[CH2:32]
Reactant: CCN(C(C)C)C(C)C
Reactant: COc1ccc(N(C)C(=O)[C@H](Cc2cccc(I)c2)NC(=O)OC(C)(C)C)cc1
Reactant: C=CCc1c(CC(=O)O)c2ccccc2n1C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Product: C=CCc1c(CC(=O)N[C@@H](Cc2cccc(I)c2)C(=O)N(C)c2ccc(OC)cc2)c2ccccc2n1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of (S)-tert-butyl 3-(3-iodophenyl)-1-((4-methoxyphenyl)(methyl)amino)-1-oxopropan-2-ylcarbamate (556 mg, 1.09 mml) in TFA (3 ml) was stirred for 10 minutes. The solvent was removed in vacuo. 2-(2-allyl-1-(tert-butoxycarbonyl)-1H-indol-3-yl)acetic acid (343 mg, 1.09 mmol), DIEA (0.38 ml, 2.18 mmol) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 414.4 mg, 1.09 mmol) were dissolved in DMF. After 10 minutes, the solution was added to TFA salt. The reaction was stirred for 2 hours at room temperature. The mixture was diluted with EtOAc (100 ml) and washed with brine (2×50 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The oily crude product was introduced to a silica gel loading column and purified by column chromatography (20-50% EtOAc/hexanes) to provide the desired product (620 mg, 0.94 mmol. MS (m/z) 660 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:9].OC[CH2:12][N:13]1[C:17](=[O:18])[CH2:16][O:15][CH-:14]1>>[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:9].[CH3:12][N:13]1[C:17](=[O:18])[CH2:16][O:15][CH-:14]1
Reactant: O=C1CO[CH-]N1CCO
Solvent: CN1CCCCCC1=O
Product: CN1[CH-]OCC1=O

Procedure:
A mercerised cotton fabric is padded with a dyeing liquor which contains, per liter, 30 g of the direct dyestuff C.I. No. 35,780 and 100 g of N-methylcaprolactam, squeezed off to a liquor pick-up of 80% and then dried for 2 minutes at 150°. It is then rinsed. A deep red dyeing is obtained. Comparably good results are obtained if instead of N-methylcaprolactam 100 g of N-hydroxyethyl-oxazolidone per liter or 150 g of N-methyloxazolidone per liter are used.
Reaction SMILES: CS[C:3](SC)=[C:4]1[C:13](=[O:14])[C:12]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:23].[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[CH:29][C:28]=1[S:41]([NH2:44])(=[O:43])=[O:42]>C1(C)C=CC=CC=1>[CH2:34]([O:33][C:30]1[CH:31]=[CH:32][C:27]2[NH:26][C:3]([C:4]3[C:13](=[O:14])[C:12]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:15][CH2:16][CH2:17][CH3:18])[C:11]4[C:6]([C:5]=3[OH:23])=[CH:7][CH:8]=[CH:9][CH:10]=4)=[N:44][S:41](=[O:42])(=[O:43])[C:28]=2[CH:29]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: Nc1ccc(OCc2ccccc2)cc1S(N)(=O)=O
Reactant: CCCCC1(CCCC)C(=O)C(=C(SC)SC)C(=O)c2ccccc21
Solvent: Cc1ccccc1
Product: CCCCC1(CCCC)C(=O)C(C2=NS(=O)(=O)c3cc(OCc4ccccc4)ccc3N2)=C(O)c2ccccc21
Temperature: 25 °C
Yield: 83.1 %

Procedure:
A solution of the product of Example 5C (52 mg, 0.14 mmol) and the product of Example 2D (38 mg, 0.14 mmol) in toluene (12 mL) was stirred at reflux for 6 hours, cooled to 25° C. and concentrated in vacuo. The residue was triturated with ether-hexane and collected by filtration to give the title compound (65 mg, 84%). 1H NMR (300 MHz, CDCl3): δ 16.66 (m, 1 H), 14.33 (s, 1 H), 8.27 (d, J=8.09 Hz, 1 H), 7.66 (m, 1 H), 7.38 (m, 10 H), 5.14 (s, 2 H), 2.35 (m, 2 H), 1.96 (m, 2 H), 1.12 (m, 4 H), 0.89 (m, 2 H), 0.70 (m, 6 H), 0.55 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH2:11])=[CH:5][C:4]=1[CH3:12].C1(N=C=NC2CCCCC2)CCCCC1.[S:28]1[CH:32]=[CH:31][CH:30]=[C:29]1[C:33]1([C:36](O)=[O:37])[CH2:35][CH2:34]1.ON1C2C=CC=CC=2N=N1.N>O1CCCC1.O.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH:11][C:36]([C:33]2([C:29]3[S:28][CH:32]=[CH:31][CH:30]=3)[CH2:35][CH2:34]2)=[O:37])=[CH:5][C:4]=1[CH3:12]
Reactant: COc1ccc(CCN)cc1C
Reactant: O=C(O)C1(c2cccs2)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: N
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1ccc(CCNC(=O)C2(c3cccs3)CC2)cc1C
Reaction time: 16 h
Yield: 81.5 %

Procedure:
A mixture of 2-(4-methoxy-3-methylphenyl)ethylamine (16 g), triethylamine (1.74 ml), 1,3-dicyclohexylcarbodiimide (8.75 g), 1-(2-thienyl)cyclopropanecarboxylic acid (7 g) and 1-hydroxybenzotriazole (5.6 g) in tetrahydrofuran (95 ml) was stirred for 16 hours. The mixture was poured into water, basified with aqueous ammonia solution and filtered. The filtrate was extracted with ethyl acetate (3×50 ml) and the combined extracts washed with 1M hydrochloric acid and brine then dried and the solvent removed in vacuo. The resulting gum was treated with acetonitrile and insoluble matter filtered off. Evaporation of the filtrate gave crude N-(2-(4-methoxy-3-methylphenyl)ethyl)-1-(2-thienyl)cyclopropanecarboxamide as a solid (10.7 g), which was used without further purification.