Triethylamine → Ethyl (S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylate

HRID 2267259Notes

Reaction equation

HRID 2267259 reaction equation
C(N(CC)CC)C.[O:8]=[C:9]1[N:15]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C@@H:25]([C:39](O)=[O:40])[CH2:26][C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[C:30]([NH2:37])=[C:29]([Cl:38])[CH:28]=3)=[O:23])[CH2:18][CH2:17]2)[CH2:14][CH2:13][C:12]2[CH:42]=[CH:43][CH:44]=[CH:45][C:11]=2[NH:10]1.[CH3:46][N:47]1[CH2:52][CH2:51][CH:50]([N:53]2[CH2:58][CH2:57][NH:56][CH2:55][C@H:54]2[C:59]([O:61][CH2:62][CH3:63])=[O:60])[CH2:49][CH2:48]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[NH2:37][C:30]1[C:31]([C:33]([F:36])([F:35])[F:34])=[CH:32][C:27]([CH2:26][C@@H:25]([O:24][C:22]([N:19]2[CH2:20][CH2:21][CH:16]([N:15]3[CH2:14][CH2:13][C:12]4[CH:42]=[CH:43][CH:44]=[CH:45][C:11]=4[NH:10][C:9]3=[O:8])[CH2:17][CH2:18]2)=[O:23])[C:39]([N:56]2[CH2:57][CH2:58][N:53]([CH:50]3[CH2:49][CH2:48][N:47]([CH3:46])[CH2:52][CH2:51]3)[C@H:54]([C:59]([O:61][CH2:62][CH3:63])=[O:60])[CH2:55]2)=[O:40])=[CH:28][C:29]=1[Cl:38]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57807633ethyl(S)-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylateHCID 58202073(R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Product 1

HCID 57807704Ethyl (S)-4-{(R)-3-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carbonyloxy]-propionyl}-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.25 mL (2.88 mmol) triethylamine were added to a mixture of 200 mg (0.36 mmol) (R)-2-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-1-carboxy-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate (Example 1f), 150 mg (0.58 mmol) ethyl(S)-1-(1-methyl-piperidin-4-yl)-piperazine-2-carboxylate (Example A10c) and 140 mg (0.44 mmol) TBTU in 2.0 mL DMF and the reaction mixture was stirred for 5 h at RT. This was purified by HPLC without any further working up; the fractions containing the product were combined and lyophilised.

Workup

  1. customThis was purified by HPLC without
  2. additionthe fractions containing the product

Sources & evidence

ORD record
ord-e8996bb178b94f0a989f2a6d65174144
Source dataset
uspto-grants-2010_12
Patent number
US07858622B2

Reaction notes

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