Diisopropylethylamine → HCID 89582307, compound

HRID 2282852Notes

Reaction equation

HRID 2282852 reaction equation
[CH3:1][O:2][C@@H:3]([C@@H:28]([N:33]([CH3:41])[C:34](=[O:40])[C@H:35]([CH:37]([CH3:39])[CH3:38])[NH2:36])[C@@H:29]([CH3:32])[CH2:30][CH3:31])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:26][CH3:27])[C@@H:13]([CH3:25])[C:14](=[O:24])[NH:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:6].[CH:42]1[C:54]2[CH:53]([CH2:55][O:56][C:57]([NH:59][CH2:60][C:61]([CH3:66])([CH3:65])[C:62](O)=[O:63])=[O:58])[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[C:46]=2[CH:45]=[CH:44][CH:43]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl.CN(C)C=O>[CH:51]1[C:52]2[CH:53]([CH2:55][O:56][C:57]([NH:59][CH2:60][C:61]([CH3:66])([CH3:65])[C:62]([NH:36][C@H:35]([C:34]([N:33]([C@@H:28]([C@@H:29]([CH3:32])[CH2:30][CH3:31])[C@H:3]([O:2][CH3:1])[CH2:4][C:5]([N:7]3[CH2:11][CH2:10][CH2:9][C@H:8]3[C@H:12]([O:26][CH3:27])[C@@H:13]([CH3:25])[C:14](=[O:24])[NH:15][CH2:16][CH2:17][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[O:6])[CH3:41])=[O:40])[CH:37]([CH3:39])[CH3:38])=[O:63])=[O:58])[C:54]3[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:47]=2[CH:48]=[CH:49][CH:50]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 450244313-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)-2,2-dimethylpropanoic acidHCID 89577620N-{(3R,4S,5S)-3-methoxy-1-[(2S)-2-{(1R,2R)-1-methoxy-2-methyl-3-oxo-3-[(2-phenylethyl)amino]propyl}pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide

Product 1

HCID 89582307HCID 89582307, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To #73 (100 mg, 0.174 mmol, 1 eq.) in dichloromethane (4 mL, 0.04 M) and N,N-dimethylformamide (0.5 mL) was added #93 (59.1 mg, 0.174 mmol, 1 eq.), followed by diisopropylethylamine (92 μL, 0.52 mmol, 3 eq.) and HATU (102 mg, 0.260 mmol, 1.5 eq.). The reaction was stirred for 18 hours and then concentrated in vacuo. The residue was taken up in ethyl acetate (6 mL) and was washed with 1 M aqueous hydrochloric acid solution (2×2 mL) and with brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel chromatography (Gradient: 0% to 50% acetone in heptane) provided #96 (102 mg, 65%) as a white solid. LC-MS: m/z 896.7 [M+H+], 918.8 [M+Na+], retention time=1.14 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic product signals: δ 7.88 (d, J=7.4 Hz, 2H), [7.83 (br dd, J=6, 5 Hz) and 8.03 (br dd, J=6, 5 Hz), total 1H], 7.67-7.73 (m, 2H), 7.36-7.48 (m, 3H), 7.22-7.35 (m, 4H), 7.13-7.21 (m, 3H), 6.86-6.96 (m, 1H), [4.44 (dd, J=8.6, 8.6 Hz) and 4.50 (dd, J=8.6, 8.6 Hz), total 1H], 3.18, 3.19, 3.26 and 3.29 (4 s, total 6H), 2.96 and 3.11 (2 br s, total 3H), 0.70-0.77 (m, 3H).

Workup

  1. concentrationconcentrated in vacuo
  2. washwas washed with 1 M aqueous hydrochloric acid solution (2×2 mL) and with brine
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by silica gel chromatography (Gradient: 0% to 50% acetone in heptane)

Sources & evidence

ORD record
ord-106a818470e74254a9761136e50b6b83
Source dataset
uspto-grants-2015_09
Patent number
US09138486B2

Reaction notes

Loading…