Diisopropylethylamine → 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-cyclopentyl-N-(2,2-dimethoxyethyl)propanamide

HRID 446445Notes

Reaction equation

HRID 446445 reaction equation
[Cl:1][C:2]1[C:15]([CH2:16][N:17]2[CH2:36][CH2:35][C:20]3([O:25][CH2:24][CH2:23][N:22]([C:26]([C:28]4[N:29]=[C:30]([CH2:33][CH3:34])[S:31][CH:32]=4)=[O:27])[CH2:21]3)[CH2:19][CH2:18]2)=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][CH2:5][O:6][CH2:7][CH2:8][C:9]([OH:11])=O.CCN(C(C)C)C(C)C.[CH3:46][O:47][CH:48]([O:56][CH3:57])[CH2:49][NH:50][CH:51]1[CH2:55][CH2:54][CH2:53][CH2:52]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:1][C:2]1[C:15]([CH2:16][N:17]2[CH2:18][CH2:19][C:20]3([O:25][CH2:24][CH2:23][N:22]([C:26]([C:28]4[N:29]=[C:30]([CH2:33][CH3:34])[S:31][CH:32]=4)=[O:27])[CH2:21]3)[CH2:35][CH2:36]2)=[CH:14][CH:13]=[CH:12][C:3]=1[CH2:4][CH2:5][O:6][CH2:7][CH2:8][C:9]([N:50]([CH:51]1[CH2:55][CH2:54][CH2:53][CH2:52]1)[CH2:49][CH:48]([O:56][CH3:57])[O:47][CH3:46])=[O:11]

Participants

6

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 581684923-(2-Chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acidHCID 58168622N-(2,2-dimethoxyethyl)cyclopentanamine

Product 1

HCID 581684603-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-cyclopentyl-N-(2,2-dimethoxyethyl)propanamideYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid (9.8 g) in DCM (100 mL) was added Hunig's Base (9.58 mL). The reaction was stirred for 10 mins before the addition of N-(2,2-dimethoxyethyl)cyclopentanamine (4.12 g) followed by HATU (7.65 g). After 1 h, the reaction mixture was diluted with DCM (200 mL) and washed with saturated sodium bicarbonate (300 mL) followed by water (300 mL). The DCM solution was dried over Na2SO4, filtered and evaporated in vacuo. The crude product was purified by silica chromatography, eluting with 2 to 5% 7N/NH3/methanol in dichloromethane to afford 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-cyclopentyl-N-(2,2-dimethoxyethyl)propanamide (12.0 g) as a pale yellow gum.

Workup

  1. washwashed with saturated sodium bicarbonate (300 mL)
  2. dry with materialThe DCM solution was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified by silica chromatography
  6. washeluting with 2 to 5% 7N/NH3/methanol in dichloromethane

Sources & evidence

ORD record
ord-93231d4d1c6b4d5b890e45989599e639
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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