Triethylamine → Ethyl(S)-1-(1-{(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}-piperidin-4-yl)-4-methyl-piperazine-2-carboxylate

HRID 2106543Notes

Reaction equation

HRID 2106543 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]([OH:41])=O)[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][N:50]([CH:53]2[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]2)[C@H:49]([C:59]([O:61][CH2:62][CH3:63])=[O:60])[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][CH:53]([N:50]3[CH2:51][CH2:52][N:47]([CH3:46])[CH2:48][C@H:49]3[C:59]([O:61][CH2:62][CH3:63])=[O:60])[CH2:54][CH2:55]2)=[O:41])=[CH:28][C:29]=1[Cl:38]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57807468ethyl(S)-4-methyl-1-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 57807426Ethyl(S)-1-(1-{(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}-piperidin-4-yl)-4-methyl-piperazine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.40 mL (2.88 mmol) triethylamine were added to a mixture of 260 mg (0.46 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), 210 mg (0.58 mmol) ethyl(S)-4-methyl-1-piperidin-4-yl-piperazine-2-carboxylate (Example A9f) and 170 mg (0.53 mmol) TBTU in 2.4 mL DMF and the reaction mixture was stirred for 18 h at RT. The reaction mixture was purified by HPLC without any further working up; the fractions containing the product were combined and lyophilised.

Workup

  1. customThe reaction mixture was purified by HPLC without
  2. additionthe fractions containing the product

Sources & evidence

ORD record
ord-46a0ccdbbbfd42a0823ce922908d6c59
Source dataset
uspto-grants-2009_08
Patent number
US07579341B2

Reaction notes

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