Triethylamine → (R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-(4-ethoxycarbonyl methyl-piperazin-1-yl)-4-methyl-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

HRID 2267256Notes

Reaction equation

HRID 2267256 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.[CH2:46]([O:48][C:49](=[O:64])[CH2:50][N:51]1[CH2:56][CH2:55][N:54]([C:57]2([CH3:63])[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH2:53][CH2:52]1)[CH3:47].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[O:8]=[C:9]1[N:15]([CH:16]2[CH2:17][CH2:18][N:19]([C:22]([O:24][C@H:25]([CH2:26][C:27]3[CH:32]=[C:31]([C:33]([F:35])([F:34])[F:36])[C:30]([NH2:37])=[C:29]([Cl:38])[CH:28]=3)[C:39]([N:60]3[CH2:61][CH2:62][C:57]([N:54]4[CH2:53][CH2:52][N:51]([CH2:50][C:49]([O:48][CH2:46][CH3:47])=[O:64])[CH2:56][CH2:55]4)([CH3:63])[CH2:58][CH2:59]3)=[O:40])=[O:23])[CH2:20][CH2:21]2)[CH2:14][CH2:13][C:12]2[CH:42]=[CH:43][CH:44]=[CH:45][C:11]=2[NH:10]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57807651Ethyl [4-(4-methyl-piperidin-4-yl)-piperazin-1-yl]acetateHCID 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 57807311(R)-1-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-2-[4-(4-ethoxycarbonyl methyl-piperazin-1-yl)-4-methyl-piperidin-1-yl]-2-oxo-ethyl 4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.10 mL (0.72 mmol) triethylamine were added to a mixture of 250 mg (0.45 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), 140 mg (0.49 mmol) ethyl[4-(4-methyl-piperidin-4-yl)-piperazin-1-yl]-acetate (Example A8b) and 160 mg (0.50 mmol) TBTU in 2 mL DMF and the reaction mixture was stirred for 18 h at RT. It was evaporated down i. vac. and the residue was purified by chromatography (Alox, gradient DCM/MeOH 40:1 nach 30:1). The fractions containing the product were combined, evaporated down i. vac. and purified by HPLC; the fractions containing the product were combined and lyophilised.

Workup

  1. customIt was evaporated down i
  2. customand the residue was purified by chromatography (Alox, gradient DCM/MeOH 40:1 nach 30:1)
  3. additionThe fractions containing the product
  4. customevaporated down i
  5. customand purified by HPLC
  6. additionthe fractions containing the product

Sources & evidence

ORD record
ord-02b6be7d497e4d19ad33a8d2039734c7
Source dataset
uspto-grants-2010_12
Patent number
US07858622B2

Reaction notes

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