Diethylamine → 2-Pyrrolidinepropanamide, 1-[(3R,4S,5S)-4-[[(2S)-2-[[(1-aminocyclopentyl)carbonyl]amino]-3-methyl-1-oxobutyl]methylamino]-3-methoxy-5-methyl-1-oxoheptyl]-I(2)-methoxy-I+/--methyl-N-[(1S)-2-phenyl-1-(2-thiazolyl)ethyl]-, (I+/-R,I(2)R,2S)-

HRID 74742Notes

Reaction equation

HRID 74742 reaction equation
C1C2C(COC([NH:18][C:19]3([C:24]([NH:26][C@H:27]([C:31]([N:33]([C@@H:35]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:36]([O:66][CH3:67])[CH2:37][C:38]([N:40]4[CH2:44][CH2:43][CH2:42][C@H:41]4[C@H:45]([O:64][CH3:65])[C@@H:46]([CH3:63])[C:47](=[O:62])[NH:48][C@H:49]([C:57]4[S:58][CH:59]=[CH:60][N:61]=4)[CH2:50][C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)=[O:39])[CH3:34])=[O:32])[CH:28]([CH3:30])[CH3:29])=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20]3)=O)C3C(=CC=CC=3)C=2C=CC=1.C(NCC)C>O1CCCC1>[NH2:18][C:19]1([C:24]([NH:26][C@H:27]([C:31]([N:33]([C@@H:35]([C@@H:68]([CH3:71])[CH2:69][CH3:70])[C@H:36]([O:66][CH3:67])[CH2:37][C:38]([N:40]2[CH2:44][CH2:43][CH2:42][C@H:41]2[C@H:45]([O:64][CH3:65])[C@@H:46]([CH3:63])[C:47](=[O:62])[NH:48][C@H:49]([C:57]2[S:58][CH:59]=[CH:60][N:61]=2)[CH2:50][C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)=[O:39])[CH3:34])=[O:32])[CH:28]([CH3:30])[CH3:29])=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23]1

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 86685730N2-[(1-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}cyclopentyl)-carbonyl]-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2-phenyl-1-(1,3-thiazol-2-yl)ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 715708742-Pyrrolidinepropanamide, 1-[(3R,4S,5S)-4-[[(2S)-2-[[(1-aminocyclopentyl)carbonyl]amino]-3-methyl-1-oxobutyl]methylamino]-3-methoxy-5-methyl-1-oxoheptyl]-I(2)-methoxy-I+/--methyl-N-[(1S)-2-phenyl-1-(2-thiazolyl)ethyl]-, (I+/-R,I(2)R,2S)-Yield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of #46 (500 mg, 0.504 mmol, 1 eq.) in tetrahydrofuran (8 mL, 0.06 M) was added diethylamine (4 mL). After stirring for 18 hours, the reaction mixture was concentrated in vacuo and the residue was purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane) to give #47 (374 mg, 96%) as a white solid. LC-MS: m/z 769.6 [M+H+], retention time=0.70 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ [8.64 (br d, J=8.4 Hz) and 8.87 (br d, J=8.6 Hz), total 1H], [8.22 (br d, J=9.4 Hz) and 8.26 (br d, J=9.4 Hz), total 1H], [7.77 (d, J=3.3 Hz) and 7.80 (d, J=3.3 Hz), total 1H], [7.63 (d, J=3.1 Hz) and 7.66 (d, J=3.3 Hz), total 1H], 7.13-7.31 (m, 5H), [5.39 (ddd, J=11.1, 8.5, 4.2 Hz) and 5.54 (ddd, J=11.7, 8.8, 4.1 Hz), total 1H], [4.53 (dd, J=9.2, 7.6 Hz) and 4.64 (dd, J=9.2, 6.6 Hz), total 1H], 3.16, 3.20, 3.21 and 3.25 (4 s, total 6H), 2.93 and 3.03 (2 br s, total 3H), [1.05 (d, J=6.8 Hz) and 1.10 (d, J=6.6 Hz), total 3H], 0.73-0.80 (m, 3H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customthe residue was purified by silica gel chromatography (Gradient: 0% to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-86b32b5c59db495081e2561e5c48a531
Source dataset
uspto-grants-2014_09
Patent number
US08828401B2

Reaction notes

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