1-Hydroxybenzotriazole → HCID 16666598, compound

HRID 562582Notes

Reaction equation

HRID 562582 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:32]=[CH:33][CH:34]=1)[C:6]([NH:8][CH2:9][C:10]([NH:12][C@@H:13]1[CH2:17][CH2:16][N:15]([CH:18]2[CH2:22][CH2:21][N:20]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][CH:24]=3)[CH2:19]2)[CH2:14]1)=[O:11])=[O:7].CN(C(ON1N=N[C:47]2C=[CH:49][CH:50]=[N:51][C:46]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.C([O-])(O)=O.[Na+]>CN(C=O)C.ClCCl>[CH2:50]([N:51]([CH2:46][CH3:47])[C:27](=[O:29])[C:26]1[CH:25]=[CH:24][C:23]([N:20]2[CH2:21][CH2:22][CH:18]([N:15]3[CH2:16][CH2:17][C@@H:13]([NH:12][C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[C:5]4[CH:32]=[CH:33][CH:34]=[C:3]([C:2]([F:36])([F:1])[F:35])[CH:4]=4)[CH2:14]3)[CH2:19]2)=[CH:31][CH:30]=1)[CH3:49]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67006887HCID 67006887, compound

Product 1

HCID 16666598HCID 16666598, compoundYield 82.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzoic acid (35 mg, 0.069 mmol), HATU (0.032 g, 0.086 mmol), N,N-diisopropylethylamine (30.2 μL, 0.173 mmol), 1-Hydroxybenzotriazole (11.7 mg, 0.0867 mmol) in DMF (3.0 mL) was added diethylame (8.25 μL, 0.079 mmol). The reaction mixture was allowed to stir at room temperature overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford, as a mixture of diastereomers, N,N-diethyl-4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzamide (32 mg, 82%) as a white solid. 1H-NMR (MeOD) δ: 1.19 (t, J=6.6 Hz, 6H), 1.66-1.80 (m, 1H), 1.90-2.05 (m, 1H), 2.18-2.40 (m, 2H), 2.50-2.70 (m, 2H), 2.80-3.06 (m, 4H), 3.15-3.40 (m, 4H), 3.38-3.60 (m, 5H), 4.03 (s, 2H), 4.37-4.50 (m, 1H), 6.58 (d, J=8.4 Hz, 2H), 7.26 (d, J=8.1 Hz, 2H), 7.69 (t, J=7.2 Hz, 1H), 7.86 (d, J=7.2 Hz, 1H), 8.14 (d, J=7.5 Hz, 1H), 8.22 (s, 1H). MS m/z: 560 (M+1)

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-23b84d2419084aa8923eaf7b0c4e08c6
Source dataset
uspto-grants-2011_11
Patent number
US08067415B2

Reaction notes

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