Phosgene → HCID 22954557, compound

HRID 1643374Notes

Reaction equation

HRID 1643374 reaction equation
[N:1]1([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:6][CH2:5][CH2:4][C@@H:3]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[NH:2]1.C(N(C(C)C)CC)(C)C.[C:33](Cl)(Cl)=[O:34].[C:37]([NH:45][NH:46][CH2:47][CH2:48][C:49]([O:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)=[O:50])(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CCCCCC.CCOC(C)=O.C1(C)C=CC=CC=1>[C:37]([NH:45][N:46]([CH2:47][CH2:48][C:49]([O:51][CH2:52][C:53]1[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=1)=[O:50])[C:33]([N:2]1[C@H:3]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4][CH2:5][CH2:6][N:1]1[C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])=[O:34])(=[O:44])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 81531Diisopropylethylamine2×HCID 110345581-Benzyl 3-tert-butyl (3S)-tetrahydropyridazine-1,3(2H)-dicarboxylateHCID 18465756HCID 18465756, compound

Product 1

HCID 22954557HCID 22954557, compoundYield 89%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (3S)-1-benzyl 3-t-butyl hexahydropyridazine-1,3-dicarboxylate (Hassall et al. J. Chem. Soc. Perkin 1, pp. 1451-1454 (1979)) (925.3 mg, 2.89 mmol) and diisopropylethylamine (0.70 ml, 4.0 mmol) in a 1.93M toluene solution of phosgene (17.96 ml, 34.7 mmol) was stirred at room temperature for 45 min, then concentrated to leave a yellow solid. To this solid was added toluene (18 ml), hydrazide (259) (861.6 mg, 2.89 mmol) and diisopropylethylamine (0.70 ml, 4.0 mmol). The mixture was stirred at room temperature for 2.75 h, then concentrated. The resulting residue was taken up in EtOAc, washed twice with 1M HCl, brine, then dried (MgSO4), filtered and concentrated to afford 2.15 g of crude material. Flash chromatography (40% EtOAc in hexane) afforded 1.65 g (89%) of the title compound as a white foam: mp 40° C.; [α]D24 −55.78° (c 0.40, CH2Cl2); IR (KBr) 3436, 2930, 1733, 1689, 1455, 1412′ 1367, 1258, 1156, 697; 1H NMR (CDCl3) δ 8.54-8.23 (0.5H, m), 7.97-7.09 (15.5H), 5.16-4.80 (4H, m), 4.66-4.32 (1H, m), 4.24-3.55 (3.3H, m), 3.50-3.26 (0.4H, m), 3.19-2.49 (2.3H, m), 2.11-1.43 (6H, m), 1.32-1.05 (7H, m); Anal. Calcd for C35H40N4O8.0.5H2O: C, 64.31; H, 6.32; N, 8.57. Found: C, 64.18; H, 6.27; N, 8.56. MS (ES+) 662 (M+Na, 84%), 645 (M++1, 100), 384 (77).

Workup

  1. concentrationconcentrated
  2. customto leave a yellow solid
  3. concentrationconcentrated
  4. washwashed twice with 1M HCl, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford 2.15 g of crude material

Sources & evidence

ORD record
ord-2232960771fb46919cbf25e8af65b6db
Source dataset
uspto-grants-2012_02
Patent number
US08119631B2

Reaction notes

Loading…