Triethylamine → HCID 22850222, compound

HRID 1379835Notes

Reaction equation

HRID 1379835 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][CH2:18][C@@H:17]([NH:26][C:27](=[O:40])[CH2:28][C:29]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH3:31])[CH3:30])[C:16]2=[O:41])=[CH:10][CH:9]=1.C(N(CC)CC)C.Cl[C:50](Cl)([O:52]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl.CCCCCC>[N:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:9]=[CH:10][C:11]([CH2:14][N:15]2[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[CH2:19][CH2:18][C@@H:17]([NH:26][C:27](=[O:40])[CH2:28][C:29]([NH:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])([CH3:31])[CH3:30])[C:16]2=[O:41])=[CH:12][CH:13]=1)=[C:50]=[O:52]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 22850215HCID 22850215, compound

Product 1

HCID 22850222HCID 22850222, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

A solution of 2.0 g (3.6 mmol) of N-[1-[[(2'-amino)[1,1'-biphenyl]-4-yl]methyl]-2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-3-t-butoxycarbonylamino-3-methylbutanamide (Example 2, Step B) and 2.0 mL of triethylamine (14 mmol) in 40 mL of methylene chloride under a nitrogen atmosphere was cooled to -10° C. and treated with 2.12 g (7.15 mmol) of triphosgene in one portion. An exotherm occurred. The reaction was stirred at room temperature for 1.5 hours when no starting amine was detected by thin layer chromatography on silica (hexanethyl acetate (1:1)). The reaction mixture was diluted with 40 mL of hexane and filtered. The filtrate was passed over 150 g of silica gel and eluted with hexane/ethyl acetate (1:1) to give 1.65 g (2.84 mmol, 79%) of the product. 1H NMR (400 MHz, CDCl3): δ 1.34 (s, 6H), 1.39 (s, 9H), 1.84 ((m, 1H), 2.40 (m, 1H), 2.49 (dd, 1H), 2.52 (m, 1H), 4.51 (m, 1H), 4.88 (d, 1H), 5.25 (d, 1H), 5.34 (br s, 1H), 6.71 (d, 1H), 7.20 (m, 12H).

Workup

  1. filtrationfiltered
  2. washeluted with hexane/ethyl acetate (1:1)

Sources & evidence

ORD record
ord-226203f708ee40609e625a518ea11843
Source dataset
uspto-grants-1997_09
Patent number
US05672596

Reaction notes

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