Hydrochloric Acid → HCID 69939673, compound

HRID 1058322Notes

Reaction equation

HRID 1058322 reaction equation
C(OC([N:8]1[CH2:39][CH2:38][CH:37]([CH2:40][CH3:41])[C@H:9]1[C:10]([N:12]1[CH2:36][CH2:35][CH2:34][C@H:13]1[C:14]([NH:16][CH2:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[CH2:25][NH:26]C(OC(C)(C)C)=O)=[O:15])=[O:11])=O)(C)(C)C.Cl>O1CCOCC1>[CH2:40]([CH:37]1[CH2:38][CH2:39][NH:8][C@@H:9]1[C:10]([N:12]1[CH2:36][CH2:35][CH2:34][C@H:13]1[C:14]([NH:16][CH2:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[CH2:25][NH2:26])=[O:15])=[O:11])[CH3:41]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 69937536HCID 69937536, compound

Product 1

HCID 69939673HCID 69939673, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred solution of diastereomer A of 1-(tert-butoxycarbonyl)-3-ethylprolyl-N-(2-{[(tert-butoxycarbonyl)amino]methyl}-5-chlorobenzyl)-L-prolinamide (34 mg, 0.06 mmol) from the previous step in dioxane (2.0 mL) at ambient temperature was added an excess of 4.0 N solution of HCl in dioxane. The reaction was monitored for completeness by LCMS. The solvent was removed in vacuo to give the HCl salt of 3-ethyl-L-prolyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide as a pale yellow oil. LCMS RT=0.74 min. LCMS (M+H)=393.3. 1H NMR (CD3OD, 400 MHz): δ 8.93 (m, 1H), 7.51 (s, 1H), 7.42-7.37 (m, 2H), 4.54-4.47 (m, 2H), 4.41-4.31 (m, 2H), 4.23 (s, 2H), 3.78-3.70 (m, 1H), 3.64-3.52 (m, 1H), 3.50-3.45 (m, 1H), 3.44-3.34 (m, 1H), 2.43 (br m, 1H), 2.34-2.27 (m, 1H), 2.16-1.67 (br m, 6H), 1.53-1.45 (m, 1H), 1.03 (t, J=7.4 Hz, 3H). Diastereomer B (37 mg, 0.06 mmol) was deprotected in similar fashion to afford the HCl salt of 3-ethyl-L-prolyl-N-[2-(aminomethyl)-5-chlorobenzyl]-L-prolinamide as a yellow oil. LCMS RT=0.73 min. LCMS (M+H)=393.3. 1H NMR (CD3OD, 400 MHz): δ 8.95 (m, 1H), 7.52 (s, 1H), 7.43-7.40 (m, 2H), 4.55 (d, J=15.6 Hz, 1H), 4.44 (dd, J=3.2 Hz, 8.8 Hz, 1H), 4.37 (d, J=15.2 Hz, 1H), 4.31 (d, J=4.8 Hz, 1H), 4.25 (s, 2H), 3.84-3.81 (m, 1H), 3.66-3.59 (m, 1H), 3.57-3.46 (m, 1H), 3.42-3.35 (m, 1H), 2.41-2.38 (m, 1H), 2.31-1.84 (m, 6H), 1.71-1.66 (m, 1H), 1.56-1.50 (m, 1H), 1.04 (t, J=7.4 Hz, 3H).

Workup

  1. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ee1b3f8eb23e4a82b1d0a2b9fbd01810
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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