Diisopropylethylamine → 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[5-[[(3-hydroxyphenyl)methyl]amino]-1H-tetrazol-1-yl]phenyl]carbonyl]-L-phenylalanine methyl ester

HRID 1976956Notes

Reaction equation

HRID 1976956 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[C:18]([N:20]2[C:24]([NH:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=3)=[N:23][N:22]=[N:21]2)[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.[CH3:34][O:35][C:36](=[O:57])[C@H:37]([CH2:39][C:40]1[CH:45]=[CH:44][C:43]([NH:46][C:47]([C:49]2[C:54]([Cl:55])=[CH:53][CH:52]=[CH:51][C:50]=2[Cl:56])=[O:48])=[CH:42][CH:41]=1)[NH2:38].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[CH3:34][O:35][C:36](=[O:57])[C@H:37]([CH2:39][C:40]1[CH:41]=[CH:42][C:43]([NH:46][C:47]([C:49]2[C:54]([Cl:55])=[CH:53][CH:52]=[CH:51][C:50]=2[Cl:56])=[O:48])=[CH:44][CH:45]=1)[NH:38][C:13]([C:12]1[CH:16]=[CH:17][C:18]([N:20]2[C:24]([NH:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([OH:33])[CH:28]=3)=[N:23][N:22]=[N:21]2)=[CH:19][C:11]=1[Cl:10])=[O:15]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 186730392-chloro-4-[5-[[(3-hydroxyphenyl)methyl]amino]-1H-tetrazol-1-yl]benzoic acidHCID 233839334-(2,6-Dichlorobenzoylamino)-L-phenylalanine methyl ester

Product 1

HCID 698493244-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[5-[[(3-hydroxyphenyl)methyl]amino]-1H-tetrazol-1-yl]phenyl]carbonyl]-L-phenylalanine methyl esterYield 75.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In an argon atmosphere, DIPEA (0.102 mL; 0.585 mmol) was added to a stirred solution of 2-chloro-4-[5-[[(3-hydroxyphenyl)methyl]amino]-1H-tetrazol-1-yl]benzoic acid (51 mg; 0.15 mmol), 4-[[(2,6-dichlorophenyl]carbonyl]amino]-L-phenylalanine methyl ester (60 mg; 0.15 mmol) and HBTU (59 mg; 0.1555 mmol) in dimethylformamide (3 mL). The reaction mixture was stirred for 17 hr at room temperature, then was concentrated under reduced pressure. The residual oil was taken up in dichloromethane (25 mL) and washed in turn with 0.5 N HCl (10 mL) and water (10 mL). The aqueous layers were backwashed in turn with dichloromethane. The combined organic layers were dried (Na2SO4) and evaporated to give 85 mg of crude product. This material was crystallized from dichloromethane-diethyl ether to furnish 79 mg of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-N-[[2-chloro-4-[5-[[(3-hydroxyphenyl)methyl]amino]-1H-tetrazol-1-yl]phenyl]carbonyl]-L-phenylalanine methyl ester as a colorless solid, mp 155-158° C. FAB HRMS: (C32H26Cl3N7O5) Obs. Mass 694.1158 Calcd. Mass 694.1139 (M+H).

Workup

  1. concentrationwas concentrated under reduced pressure
  2. washwashed in turn with 0.5 N HCl (10 mL) and water (10 mL)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. customevaporated
  5. customto give 85 mg of crude product
  6. customThis material was crystallized from dichloromethane-diethyl ether

Sources & evidence

ORD record
ord-1f118029628348c8a651496712a71be3
Source dataset
uspto-grants-2001_05
Patent number
US06229011B1

Reaction notes

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