Potassium Carbonate → (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-1-[4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butan-1,4-dione

HRID 736944Notes

Reaction equation

HRID 736944 reaction equation
[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH:3]1[CH2:4][CH:5]([N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)[CH2:6]2.[NH2:16][C:17]1[C:48]([C:49]([F:52])([F:51])[F:50])=[CH:47][C:20]([CH2:21][C@@H:22]([CH2:26][C:27](=[O:46])[N:28]2[CH2:33][CH2:32][CH:31]([N:34]3[CH2:40][CH2:39][C:38]4[CH:41]=[CH:42][CH:43]=[CH:44][C:37]=4[NH:36][C:35]3=[O:45])[CH2:30][CH2:29]2)[C:23](O)=[O:24])=[CH:19][C:18]=1[Cl:53].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:16][C:17]1[C:48]([C:49]([F:51])([F:50])[F:52])=[CH:47][C:20]([CH2:21][C@@H:22]([CH2:26][C:27]([N:28]2[CH2:33][CH2:32][CH:31]([N:34]3[CH2:40][CH2:39][C:38]4[CH:41]=[CH:42][CH:43]=[CH:44][C:37]=4[NH:36][C:35]3=[O:45])[CH2:30][CH2:29]2)=[O:46])[C:23]([N:13]2[CH2:14][CH2:15][N:10]([CH:5]3[CH2:6][CH:7]4[N:2]([CH3:1])[CH:3]([CH2:9][CH2:8]4)[CH2:4]3)[CH2:11][CH2:12]2)=[O:24])=[CH:19][C:18]=1[Cl:53]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 154797638-Methyl-3-(piperazin-1-yl)-8-azabicyclo[3.2.1]octaneHCID 68591515(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid

Product 1

HCID 57848362(S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-1-[4-(8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-piperazin-1-yl]-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butan-1,4-dione

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

850 mg (2.4 mmol) 8-methyl-3-piperazin-1-yl-8-aza-bicyclo[3.2.1]octan were added to a solution of 1.04 g (1.88 mmol) (S)-2-(4-amino-3-chloro-5-trifluoromethyl-benzyl)-4-oxo-4-[4-(2-oxo-1,2,4,5-tetrahydro-1,3-benzodiazepin-3-yl)-piperidin-1-yl]-butanoic acid, 642 mg (2.0 mmol) TBTU and 1.64 mL (9.6 mmol) ethyldiisopropylamine in 20 mL DMF and the reaction mixture was stirred overnight at RT. The reaction solution was combined with 15% K2CO3 solution, stirred for 10 min at RT, the precipitated substance was suction filtered, washed with 50 mL water and dried in the air and purified by chromatography (silica gel, gradient: DCM to DCM/MeOH/NH3 10:85:5).

Workup

  1. stirringstirred for 10 min at RT
  2. filtrationfiltered
  3. washwashed with 50 mL water
  4. customdried in the air
  5. custompurified by chromatography (silica gel, gradient: DCM to DCM/MeOH/NH3 10:85:5)

Sources & evidence

ORD record
ord-c956c973a81b48c2b944cc644a99fbc9
Source dataset
uspto-grants-2009_09
Patent number
US07595312B2

Reaction notes

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