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

HRID 1255318Notes

Reaction equation

HRID 1255318 reaction equation
CN([C:4]([O:8]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[C:39]([CH2:40][N:41]2[CH2:60][CH2:59][C:44]3([O:49][CH2:48][CH2:47][N:46]([C:50]([C:52]4[N:53]=[C:54]([CH2:57][CH3:58])[S:55][CH:56]=4)=[O:51])[CH2:45]3)[CH2:43][CH2:42]2)=[CH:38][CH:37]=[CH:36][C:27]=1[CH2:28][CH2:29][O:30][CH2:31][CH2:32]C(O)=O.CCN(C(C)C)C(C)C.[CH2:70]([NH:72][CH2:73][CH:74]([O:77][CH3:78])[O:75][CH3:76])[CH3:71]>CN(C=O)C>[Cl:25][C:26]1[C:39]([CH2:40][N:41]2[CH2:60][CH2:59][C:44]3([O:49][CH2:48][CH2:47][N:46]([C:50]([C:52]4[N:53]=[C:54]([CH2:57][CH3:58])[S:55][CH:56]=4)=[O:51])[CH2:45]3)[CH2:43][CH2:42]2)=[CH:38][CH:37]=[CH:36][C:27]=1[CH2:28][CH2:29][O:30][CH2:31][CH2:32][C:4]([N:72]([CH2:73][CH:74]([O:77][CH3:78])[O:75][CH3:76])[CH2:70][CH3:71])=[O:8]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 3020444N-ethyl-2,2-dimethoxyethanamineHCID 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 acid

Product 1

HCID 581684943-(2-Chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)-N-(2,2-dimethoxyethyl)-N-ethylpropanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (1.06 g) was added 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 [Example 26, step e] (0.75 g), Hunig's base (1.22 mL) and N-ethyl-2,2-dimethoxyethanamine [U.S. Pat. No. 2,707,186] (0.37 g) in DMF (5 mL). The resulting dark solution was stirred overnight at RT. The reaction mixture was partitioned between ethyl acetate (25 mL) and 20% brine (25 mL). The organic layer was separated and washed with 20% brine (2×25 mL). The organic solution was evaporated and the residue purified by silica gel chromatography, gradient elution isohexane:triethylamine 95:5 to ethyl acetate:triethylamine 95:5. The fractions containing the product were combined and evaporated to give the subtitled compound as an oil. Yield 0.70 g.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (25 mL) and 20% brine (25 mL)
  2. customThe organic layer was separated
  3. washwashed with 20% brine (2×25 mL)
  4. customThe organic solution was evaporated
  5. customthe residue purified by silica gel chromatography, gradient elution isohexane:triethylamine 95:5 to ethyl acetate:triethylamine 95:5
  6. additionThe fractions containing the product
  7. customevaporated

Sources & evidence

ORD record
ord-63f9233f10ef42e2b7ed9b55cd871944
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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