Diisopropylethylamine → HCID 57453594, compound

HRID 2081130Notes

Reaction equation

HRID 2081130 reaction equation
Cl.[Cl:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][N:6]([C:12]([O:14][C@@H:15]1[CH2:19][C@@H:18]([C:20]([O:22][CH3:23])=[O:21])[NH:17][CH2:16]1)=[O:13])[CH2:7]2.[C:24]([O:28][C:29]([C@@H:31]([C:35]([CH3:38])([CH3:37])[CH3:36])[C:32](O)=[O:33])=[O:30])([CH3:27])([CH3:26])[CH3:25].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>CC#N>[Cl:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][N:6]([C:12]([O:14][C@@H:15]1[CH2:19][C@@H:18]([C:20]([O:22][CH3:23])=[O:21])[N:17]([C:32](=[O:33])[C@@H:31]([C:29]([O:28][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:30])[C:35]([CH3:38])([CH3:37])[CH3:36])[CH2:16]1)=[O:13])[CH2:7]2

Participants

6

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 57437884HCID 57437884, compoundHCID 57463503HCID 57463503, compound

Product 1

HCID 57453594HCID 57453594, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A 200 mL round-bottomed flask was charged with (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-chloroisoindoline-2-carboxylate hydrochloride (1.20 g, 3.32 mmol), (S)-2-(tert-butoxycarbonyl)-3,3-dimethylbutanoic acid (807 mg, 3.49 mmol) and HATU (1.90 g, 4.98 mmol) in dry MeCN (30 mL). The solution was then cooled on an ethanol-ice bath and treated with DIEA (1.74 mL, 9.97 mmol) by dropwise addition. The mixture was stirred at 0° C. for 1 h, then allowed to warm up and stirred at room temperature for 16 h. The mixture was then concentrated and the residue dissolved in EtOAc (100 mL) and washed with iced 5% citric acid (aq.) (3×30 mL), 1M NaOH (3×30 mL), water (3×30 mL) and brine (3×30 mL). The organic layer was dried over MgSO4, filtered and concentrated to an oil. The oil was purified by chromatography (Biotage) eluting with 35% EtOAc-hexanes to give the product as a white foam, 1.27 g, 71%. MS m/e 438 (M+H)+−Boc. 1H NMR (400 MHz, d6-DMSO) δ 7.3-7.4 (m, 3H), 6.7-6.76 (m, 1H), 5.24 (bs, 1H), 4.4-4.76 (m, 4H), 4.12-4.2 (m, 1H), 3.96-4.3 (m, 1H), 3.7-3.78 (m, 1H), 3.64 (d, 3H), 2.38-2.48 (m, 1H), 2.07-2.16 (m, 1H), 1.14 (d, 9H), 0.98 (s, 9H).

Workup

  1. temperatureThe solution was then cooled on an ethanol-ice bath
  2. temperatureto warm up
  3. stirringstirred at room temperature for 16 h
  4. concentrationThe mixture was then concentrated
  5. dissolutionthe residue dissolved in EtOAc (100 mL)
  6. washwashed with iced 5% citric acid (aq.) (3×30 mL), 1M NaOH (3×30 mL), water (3×30 mL) and brine (3×30 mL)
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe oil was purified by chromatography (Biotage)
  11. washeluting with 35% EtOAc-hexanes

Sources & evidence

ORD record
ord-75ebeccd668d4988b47f839d98fdfa6d
Source dataset
uspto-grants-2011_04
Patent number
US07932277B2

Reaction notes

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