Diisopropylethylamine → HCID 90183093, compound

HRID 1499306

Reaction equation

HRID 1499306 reaction equation
[CH3:1][C:2]1[CH:21]=[CH:20][C:19]([C@H:22]2[C@H:27]([OH:28])[C@@H:26]([OH:29])[C@H:25]([OH:30])[C@@H:24]([S:31][CH3:32])[O:23]2)=[CH:18][C:3]=1[CH2:4][C:5]1[CH:17]=[CH:16][C:8]([O:9][CH2:10][CH2:11][CH2:12][C:13](O)=[O:14])=[CH:7][CH:6]=1.[NH2:33][C:34]1([C:39]([NH2:41])=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1[CH:21]=[CH:20][C:19]([C@H:22]2[C@H:27]([OH:28])[C@@H:26]([OH:29])[C@H:25]([OH:30])[C@@H:24]([S:31][CH3:32])[O:23]2)=[CH:18][C:3]=1[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([O:9][CH2:10][CH2:11][CH2:12][C:13]([NH:33][C:34]2([C:39]([NH2:41])=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35]2)=[O:14])=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111160861-AminocyclopentanecarboxamideHCID 76071230HCID 76071230, compound

Product 1

HCID 90183093HCID 90183093, compoundYield 61.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenoxy)butanoic acid (39, 46 mg, 0.10 mmol), 1-aminocyclopentanecarboxamide (26 mg, 0.20 mmol), HATU (57 mg, 0.15 mmol), and DIPEA (52 μL, 0.30 mmol) were combined in DMF (0.5 mL) and stirred overnight at room temperature. The reaction was diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine (with back extraction), dried over MgSO4, filtered, and concentrated under vacuum. The material was purified by prep HPLC (C18 30×100 mm column, 20-60% CH3CN/10 mM aqueous ammonium formate, 45 mL/min) and lyophilized to give 35 mg (61% yield) of amide 41 as a white solid. 1H NMR (400 MHz, MeOH-d4) δ ppm 7.10-7.19 (m, 3 H), 7.04 (d, J=8.6 Hz, 2 H), 6.81 (m, J=8.6 Hz, 2 H), 4.39 (d, J=9.3 Hz, 1 H), 4.12 (d, J=9.1 Hz, 1 H), 3.96 (t, J=6.2 Hz, 2 H), 3.92 (s, 2 H), 3.34-3.50 (m, 3 H), 2.41 (t, J=7.5 Hz, 2 H), 2.12-2.22 (m, 8 H), 2.04 (quin, J=6.9 Hz, 2 H), 1.93 (dt, J=12.8, 5.1 Hz, 2 H), 1.64-1.75 (m, 4H); MS (ES+) [M+H]+=573.

Workup

  1. washwashed with saturated aqueous NaHCO3 and brine (with back extraction)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe material was purified by prep HPLC (C18 30×100 mm column, 20-60% CH3CN/10 mM aqueous ammonium formate, 45 mL/min)

Sources & evidence

ORD record
ord-edde42b6a1864c0aaff8d8791371a0dc
Source dataset
uspto-grants-2015_12
Patent number
US09200025B2

Linked notes

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