4-Methylmorpholine → HCID 22881852, compound

HRID 1385886Notes

Reaction equation

HRID 1385886 reaction equation
[C:1]([C:4]1[CH:39]=[CH:38][C:7]([C:8]([NH:10][C@H:11]([C:15]([N:17]2[CH2:37][CH2:36][CH2:35][C@H:18]2[C:19]([NH:21][CH:22]([CH:32]([CH3:34])[CH3:33])[C:23](=[O:31])[C:24]([F:30])([F:29])[C:25]([F:28])([F:27])[F:26])=[O:20])=[O:16])[CH:12]([CH3:14])[CH3:13])=[O:9])=[CH:6][CH:5]=1)(O)=[O:2].C(Cl)(=O)C(Cl)=O.[CH3:46][NH:47][CH2:48][CH2:49][N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1.CN1CCOCC1>CN(C=O)C>[CH3:46][N:47]([CH2:48][CH2:49][N:50]1[CH2:55][CH2:54][O:53][CH2:52][CH2:51]1)[C:1]([C:4]1[CH:39]=[CH:38][C:7]([C:8]([NH:10][C@H:11]([C:15]([N:17]2[CH2:37][CH2:36][CH2:35][C@H:18]2[C:19]([NH:21][CH:22]([CH:32]([CH3:34])[CH3:33])[C:23](=[O:31])[C:24]([F:29])([F:30])[C:25]([F:27])([F:26])[F:28])=[O:20])=[O:16])[CH:12]([CH3:14])[CH3:13])=[O:9])=[CH:6][CH:5]=1)=[O:2]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 14979282Methyl(2-(morpholin-4-yl)ethyl)amineHCID 44360133N-{(S)-2-Methyl-1-[(S)-2-(3,3,4,4,4-pentafluoro-1-isopropyl-2-oxo-butylcarbamoyl)-pyrrolidine-1-carbonyl]-propyl}-terephthalamic acid

Product 1

HCID 22881852HCID 22881852, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

The acid of Example 13 (b) (0.36 g, 0.64 mmol) was activated with oxalyl chloride (0.07 mL, 0.83 mmol) and DMF (3 drops) and coupled with 4-[2-(methylamino)ethyl]-morpholine (92 mg, 0.64 mmol) using NMM (0.14 mL, 1.28 mmol) according to the method described in Example 5 (h). Purification by flash chromatography (75:25 acetone:EtOAc) gave 0.25 g (57%) of the title compound (7:1 L-L-L:L-L-D) as an off-white foam. TLC: Rf 0.19 (3:1 acetone:EtOAc). 1H NMR (partial): δ7.88-7.82 and 7.52-7.46 (pr m, 4H, aryl), 7.42 (br d, J=7.6 Hz, 1H, NH), 6.84 (br d, J=8.8 Hz, 1H, NH), 5.02-4.96 (m, 1H, CH), 4.85 (dd, J=8.6, 7.0 Hz, 1H, CH), 4.72 (dd, J=8.0, 2.0 Hz, 1/8H, CH of Pro), 4.6 (dd, J=8.1, 2.9 Hz, 7/8H, CH of Pro), 1.14-0.82 (m, 12H, 4×CH3). 19F NMR: δ−82.12 (s, CF3, major isomer), −82.15 (s, CF3, minor isomer), −121.52 and −122.70 (AB quartet, J=294 Hz, CF2, minor isomer), −121.54 and −122.58 (AB quartet, J=294 Hz, CF2, major isomer). MS (DCI/CH4): m/z (rel intensity) 691 (26), 690 (MH+, 100), 374 (62), 317 (18), 113 (22), 100 (43), 84 (36), 83 (23). HRMS (C32H45F5N5O6) (MH+): calcd, 690.3290; obsd, 690.3274.

Workup

  1. customPurification by flash chromatography (75:25 acetone:EtOAc)

Sources & evidence

ORD record
ord-7b685d630e8044fc94466d3a4e5a68dd
Source dataset
uspto-grants-2001_07
Patent number
US06265381B1

Reaction notes

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