Diisopropylethylamine → Trifluoroacetic acid

HRID 228093Notes

Reaction equation

HRID 228093 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([O:32][CH2:33][CH2:34][CH2:35][NH2:36])=[O:31])[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.C(OC(=O)NCCCO)(C)(C)C.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[OH:70][C:71]([C:73]([F:76])([F:75])[F:74])=[O:72].N[C@H](CC1C=CC(Cl)=CC=1)C(N1CCN(C2C=CC=CC=2NS(C)(=O)=O)CC1)=O>>[C:71]([OH:72])([C:73]([F:76])([F:75])[F:74])=[O:70].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:29][C:30]([O:32][CH2:33][CH2:34][CH2:35][NH2:36])=[O:31])[C:10]([N:12]2[CH2:13][CH2:14][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH2:16][CH2:17]2)=[O:11])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 3838134tert-butyl N-(3-hydroxypropyl)carbamateHCID 21060079HCID 21060079, compoundHCID 86590295HCID 86590295, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 21060079HCID 21060079, compound

Procedure

Following the procedure of Example 51, N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)-amino]phenyl}piperazinyl)-2-oxoethyl](3-aminopropoxy)carboxamide, was prepared from N-(3-hydroxypropyl)-carbamic acid tert-butyl ester (Aldrich) (40 mg, 0.230 mmol), triphosgene (Avocado) (30 mg, 0.1 mmol), DIEA (0.040 mL, 0.230 mmol), (2R)-2-amino-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)propan-1-one TFA salt (200 mg, 0.36 mmol), and more DIEA (0.34 mL, 2.0 mmol). The Boc protecting group was removed by treating with a soln of 50% TFA in CH2Cl2 (2 mL) for 2 h. The crude product was purified by preparative TLC (60% hexane, 38% CH2Cl2 and 2% 2N NH3 in MeOH) and then by preparative HPLC (TFA buffer) to afford the title compound (TFA salt) as a white solid (10 mg). MS (ESI, pos. ion) m/z: 538 (M+H); MS (ESI, neg. ion) m/z: 536 (M−H). Calc'd for C24H32ClN5O5S: 537.18.

Workup

  1. customThe Boc protecting group was removed
  2. additionby treating with a soln of 50% TFA in CH2Cl2 (2 mL) for 2 h
  3. customThe crude product was purified by preparative TLC (60% hexane, 38% CH2Cl2 and 2% 2N NH3 in MeOH)

Sources & evidence

ORD record
ord-d1b6fd840f814971a4479fa734955a18
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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