Ethanolamine → HCID 18651505, compound

HRID 1033416Notes

Reaction equation

HRID 1033416 reaction equation
[CH3:1][C:2]([NH:36][C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38])([CH3:35])[CH2:3][C:4]([NH:6][C@@H:7]1[CH2:13][CH2:12][C:11]2[CH:14]=[CH:15][CH:16]=[CH:17][C:10]=2[N:9]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[C:26]([C:31]([OH:33])=O)=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:21][CH:20]=2)[C:8]1=[O:34])=[O:5].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[CH2:81]([CH2:83][NH2:84])[OH:82]>C(Cl)Cl.C(OCC)(=O)C>[OH:82][CH2:81][CH2:83][NH:84][C:31]([C:26]1[C:25]([C:22]2[CH:23]=[CH:24][C:19]([CH2:18][N:9]3[C:10]4[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=4[CH2:12][CH2:13][C@@H:7]([NH:6][C:4](=[O:5])[CH2:3][C:2]([NH:36][C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)=[O:38])([CH3:35])[CH3:1])[C:8]3=[O:34])=[CH:20][CH:21]=2)=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:33]

Participants

7

Reactant 4

HCID 700EthanolamineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67751249HCID 67751249, compound

Product 1

HCID 18651505HCID 18651505, compoundYield 79.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 70 mg (0.11 mmol) of 4'-[[2,3,4,5-tetrahydro-3(R)-[[3-methyl-1-oxo-3-[(benzyloxycarbonyl)amino]butyl]amino]-2-oxo-1H-1-benzazepin-1-yl]methyl][1,1'-biphenyl]-2-carboxylic acid (Example 72, Step B) in 2 mL of dry methylene chloride under nitrogen at 0° C. was added 0.023 mL (0.17 mmol) of triethylamine followed by 55 mg (0.12 mmol) of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate. After 5 minutes, 0.010 mL (0.33 mmol) of ethanolamine was added to the reaction by syringe. The reaction mixture was slowly warmed to room temperature. After 2 hours, the reaction was diluted with 75 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/methanol (97:3) to afford 58 mg (78%) of the product as a white foam. 1H NMR (200 MHz,CDCl3): 1.30 (s,3H), 1.35 (s,3H), 1.80 (m,1H), 2.20-2.75 (m,7H), 3.10-3.40 (m,4H), 4.51 (m,1H), 4.92 (d, 14 Hz, 1H), 5.00 (s,2H), 5.10 (d,14 Hz, 1H), 5.68 (s, 1H), 6.53 (d,6 Hz, 1H), 7.12-7.48 (m,16H), 7.65 (d;1.6 Hz;1H). FAB-MS: calculated for C39H42N4O6 662; found 686 (M+Na).

Workup

  1. waitAfter 2 hours
  2. washwashed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent removed under vacuum
  6. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate/methanol (97:3)

Sources & evidence

ORD record
ord-ce4f43eefd85458b9ec34249af5e715a
Source dataset
uspto-grants-1994_05
Patent number
US05310737

Reaction notes

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