1-Hydroxybenzotriazole → HCID 59547283, compound

HRID 2038573Notes

Reaction equation

HRID 2038573 reaction equation
[NH2:1][CH2:2][C:3]1([CH2:22][C:23]([OH:25])=O)[CH2:7][C@@H:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[N:5]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:4]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[O:25]=[C:23]1[CH2:22][C:3]2([CH2:4][N:5]([C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[C@H:6]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:7]2)[CH2:2][NH:1]1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59547332HCID 59547332, compound

Product 1

HCID 59547283HCID 59547283, compoundYield 59.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of amino acid 2-((5S)-3-(aminomethyl)-1,5-bis(tert-butoxycarbonyl)pyrrolidin-3-yl)acetic acid (D6) (1.45 mmol) in CH2Cl2 (32 ml) was added 1-hydroxybenzotriazole (HOBT, 196 mg, 1.45 mmol, 1 eq), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 418 mg, 2.2 mmol, 1.5 eq), and N,N-Diisopropylethylamine (DIEA, 756 μl, 4.4 mmol, 3.0 eq). The reaction was aged at room temp. overnight. The solution was diluted with CH2Cl2 (100 ml) and washed with water (100 ml), 1N sodium hydroxide in water (100 ml) and brine (100 ml). The organics were dried over sodium sulfate, filtered, and concentrated with a second extract, to give crude product. This was purified on silica (1% to 20% MeOH/CH2Cl2 gradient) to give spirolactam (3S)-di-tert-butyl 8-oxo-2,7-diazaspiro[4.4]nonane-2,3-dicarboxylate (E6) (295 mg, 868 μmol). 1H NMR (CDCl3) δ1.35 (m, 18H), 1.91 (m, 2H), 2.3 (m, 3H), 3.2 (m, 2H), 3.3-3.5 (m, 2H), 4.10 (m, 1H), 6.21 (m, 1H); LCMS for C17H28N2O5 340.20 [M], found ES+ 341.2 [M+H]+, 285.2 [M+H, minus t-butyl]+, 285.2 [M+H, minus t-butyl, minus BOC]+ at 2.6 minutes retention time, using 10-90% acetonitrile/water (with 0.1% formic acid buffer) gradient over 5 minutes.

Workup

  1. washwashed with water (100 ml), 1N sodium hydroxide in water (100 ml) and brine (100 ml)
  2. dry with materialThe organics were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated with a second extract
  5. customto give crude product
  6. customThis was purified on silica (1% to 20% MeOH/CH2Cl2 gradient)

Sources & evidence

ORD record
ord-d288bf917f0b4bd4840f67269f252b57
Source dataset
uspto-grants-2013_11
Patent number
US08575208B2

Reaction notes

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