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 446440Notes

Reaction equation

HRID 446440 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. m/z 651 M+ (APCI).

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-0840313e156a484db94736f04ccbf967
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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