Water → N-Butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide monosulphate salt

HRID 446463Notes

Reaction equation

HRID 446463 reaction equation
[CH2:1]([N:5]([CH2:42][CH2:43][NH:44][CH2:45][CH2:46][C:47]1[C:52]2[O:53][CH2:54][C:55](=[O:57])[NH:56][C:51]=2[C:50]([OH:58])=[CH:49][CH:48]=1)[C:6](=[O:41])[CH2:7][CH2:8][O:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][N:20]2[CH2:40][CH2:39][C:23]3([O:28][CH2:27][CH2:26][N:25]([C:29]([C:31]4[N:32]=[C:33]([CH:36]([CH3:38])[CH3:37])[S:34][CH:35]=4)=[O:30])[CH2:24]3)[CH2:22][CH2:21]2)[CH:13]=1)[CH2:2][CH2:3][CH3:4].[S:59](=[O:63])(=[O:62])([OH:61])[OH:60].O>CCO.CC#N>[S:59]([OH:63])([OH:62])(=[O:61])=[O:60].[CH2:1]([N:5]([CH2:42][CH2:43][NH:44][CH2:45][CH2:46][C:47]1[C:52]2[O:53][CH2:54][C:55](=[O:57])[NH:56][C:51]=2[C:50]([OH:58])=[CH:49][CH:48]=1)[C:6](=[O:41])[CH2:7][CH2:8][O:9][CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH2:19][N:20]2[CH2:40][CH2:39][C:23]3([O:28][CH2:27][CH2:26][N:25]([C:29]([C:31]4[N:32]=[C:33]([CH:36]([CH3:37])[CH3:38])[S:34][CH:35]=4)=[O:30])[CH2:24]3)[CH2:22][CH2:21]2)[CH:13]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 51036603N-Butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide

Product 1

HCID 86651693N-Butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide monosulphate salt

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

N-butyl-N-(2-(2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethylamino)ethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide (limiting reagent) was dissolved in EtOH (15 vols) and 4.9M sulphuric acid (1 molar equivalent) was added and the solution was stirred at room temp for 48 hours. The precipitate was collected, washed with EtOH (1 vol) and vacuum dried (oven at 40° C., oil pump) to leave a white solid (70% recovery). 5% water in MeCN (20 volumes) was added and the mixture stirred for 6 days. Crystalline solid (form G) was then collect by filtration (95% recovery).

Workup

  1. customThe precipitate was collected
  2. washwashed with EtOH (1 vol) and vacuum
  3. customdried (oven at 40° C., oil pump)
  4. customto leave a white solid (70% recovery)
  5. stirringthe mixture stirred for 6 days
  6. filtrationCrystalline solid (form G) was then collect by filtration (95% recovery)

Sources & evidence

ORD record
ord-dc34ce348bfa4013876303944cf2e840
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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