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

HRID 446432Notes

Reaction equation

HRID 446432 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:25][C:26]1[C:39]([CH2:40][N:41]2[CH2:61][CH2:60][C:44]3([O:49][CH2:48][CH2:47][N:46]([C:50]([C:52]4[N:53]=[C:54]([CH:57]([CH3:59])[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:33](O)=[O:34].CCN(C(C)C)C(C)C.[CH3:71][O:72][CH:73]([O:83][CH3:84])[CH2:74][NH:75][CH:76]1[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78][CH2:77]1>CN(C=O)C>[CH:76]1([N:75]([CH2:74][CH:73]([O:83][CH3:84])[O:72][CH3:71])[C:33](=[O:34])[CH2:32][CH2:31][O:30][CH2:29][CH2:28][C:27]2[CH:36]=[CH:37][CH:38]=[C:39]([CH2:40][N:41]3[CH2:42][CH2:43][C:44]4([O:49][CH2:48][CH2:47][N:46]([C:50]([C:52]5[N:53]=[C:54]([CH:57]([CH3:59])[CH3:58])[S:55][CH:56]=5)=[O:51])[CH2:45]4)[CH2:60][CH2:61]3)[C:26]=2[F:25])[CH2:82][CH2:81][CH2:80][CH2:79][CH2:78][CH2:77]1

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 59224582N-(2,2-dimethoxyethyl)cycloheptanamineHCID 669637983-(2-Fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid

Product 1

HCID 58168473N-Cycloheptyl-N-(2,2-dimethoxyethyl)-3-(2-fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of HATU (0.143 g) in DMF (0.5 mL) was added to a solution of 3-(2-fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid [Example 7, step d] (0.133 g), Hunig's base (0.22 mL) and N-(2,2-dimethoxyethyl)cycloheptanamine [WO 2008075025] (0.050 g) in DMF (0.5 mL). The resulting dark solution was stirred overnight at RT. The solvent was evaporated and the residue partitioned between ethyl acetate (25 mL) and 20% aqueous brine (25 mL). The organic layer was separated and washed with 20% aqueous brine (2×25 mL). The organic solution was evaporated and the residue purified by silica gel chromatography, elution gradient 65:30:5 to 47.5:47.5:5 isohexane:ethyl acetate:triethylamine. The fractions containing the product were combined and evaporated to give the subtitled compound as an oil. Yield 0.165 g.

Workup

  1. customThe solvent was evaporated
  2. customthe residue partitioned between ethyl acetate (25 mL) and 20% aqueous brine (25 mL)
  3. customThe organic layer was separated
  4. washwashed with 20% aqueous brine (2×25 mL)
  5. customThe organic solution was evaporated
  6. customthe residue purified by silica gel chromatography, elution gradient 65:30:5 to 47.5:47.5:5 isohexane
  7. additionThe fractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-acf43fcc5d78489da7e6db6f7b73b9c9
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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