Diisopropylethylamine → n-[(1r)-2-(4-{2-[(2-Aminoethyl)amino]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide

HRID 228107Notes

Reaction equation

HRID 228107 reaction equation
CCN(C(C)C)C(C)C.C(OC([NH:17][CH2:18][CH2:19][NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][N:30]([C:33](=[O:63])[C@H:34]([NH:43][C:44]([C@@H:46]2[CH2:55][C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH2:48][N:47]2C(OC(C)(C)C)=O)=[O:45])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)[CH2:29][CH2:28]1)=O)(C)(C)C.NC1C=CC=CC=1N1CCN(C(=O)[C@H](NC([C@@H]2CC3C(=CC=CC=3)CN2C(OC(C)(C)C)=O)=O)CC2C=CC(Cl)=CC=2)CC1.C(OC(=O)NCC=O)(C)(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl>[NH2:17][CH2:18][CH2:19][NH:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:28][CH2:29][N:30]([C:33](=[O:63])[C@H:34]([NH:43][C:44]([C@@H:46]2[CH2:55][C:54]3[C:49](=[CH:50][CH:51]=[CH:52][CH:53]=3)[CH2:48][NH:47]2)=[O:45])[CH2:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)[CH2:31][CH2:32]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 58714321tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylateHCID 69073578tert-butyl 3-[N-((1R)-2-{4-[2-({2-[(tert-butoxy) carbonylamino]ethyl}amino)phenyl]piperazinyl}-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl](3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 10166491n-[(1r)-2-(4-{2-[(2-Aminoethyl)amino]phenyl}piperazinyl)-1-[(4-chlorophenyl)methyl]-2-oxoethyl]((3s)(3-1,2,3,4-tetrahydroisoquinolyl))carboxamide

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

Following the procedure for the synthesis of Example 40 Step 3 (without DIEA), tert-butyl 3-[N-((1R)-2-{4-[2-({2-[(tert-butoxy)carbonylamino]ethyl}amino)phenyl]-piperazinyl}-1-[(4-chlorophenyl)methyl]-2-oxoethyl)-carbamoyl](3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from tert-butyl 3-(N-{(1R)-2-[4-(2-aminophenyl)piperazinyl]-1-[(4-chlorophenyl)-methyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate (Preparation IX) (630 mg, 1.0 mmol) in 2 mL of ClCH2CH2Cl, tert-butyl-N-(2-oxoethyl)carbamate (179 mg, 1.126 mmol) (Aldrich) in ClCH2CH2Cl (10 mL), and NaBH(OAc)3 (330 mg, 1.557 mmol) (Aldrich). The crude was purified by flash chromatography (SiO2, 2:1 hexane:EtOAc) to afford the desired compound (578 mg). MS (ESI, pos. ion) m/z: 761 (M+H), (ESI, neg. ion) m/z: 759 (M−H). Calc'd for C41H53ClN6O6: 761.35. Anal. Calc'd for C41H53ClN6O6-0.5 C4H8O2-0.5 H2O: C, 63.42; H, 7.18; N, 10.32; Cl, 4.35. Found C, 62.96 (+0.46); H, 7.14; N, 10.26; Cl, 4.06.

Workup

  1. customThe crude was purified by flash chromatography (SiO2, 2:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-1e9a26987a9d4e7f8888b280bb45151f
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

Loading…