Sodium Bicarbonate → 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

HRID 1255342Notes

Reaction equation

HRID 1255342 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:13]([N:17]([CH2:54][CH:55](OC)OC)[C:18](=[O:53])[CH2:19][CH2:20][O:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH2:31][N:32]2[CH2:52][CH2:51][C:35]3([O:40][CH2:39][CH2:38][N:37]([C:41]([C:43]4[N:44]=[C:45]([CH:48]([CH3:50])[CH3:49])[S:46][CH:47]=4)=[O:42])[CH2:36]3)[CH2:34][CH2:33]2)[CH:25]=1)[CH2:14][CH2:15][CH3:16].Cl.[NH2:61][CH2:62][CH2:63][C:64]1[C:69]2[O:70][CH2:71][C:72](=[O:74])[NH:73][C:68]=2[C:67]([OH:75])=[CH:66][CH:65]=1.C(=O)(O)[O-].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.CN1C(=O)CCC1.O>[CH2:13]([N:17]([CH2:54][CH2:55][NH:61][CH2:62][CH2:63][C:64]1[C:69]2[O:70][CH2:71][C:72](=[O:74])[NH:73][C:68]=2[C:67]([OH:75])=[CH:66][CH:65]=1)[C:18](=[O:53])[CH2:19][CH2:20][O:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH2:31][N:32]2[CH2:52][CH2:51][C:35]3([O:40][CH2:39][CH2:38][N:37]([C:41]([C:43]4[N:44]=[C:45]([CH:48]([CH3:49])[CH3:50])[S:46][CH:47]=4)=[O:42])[CH2:36]3)[CH2:34][CH2:33]2)[CH:25]=1)[CH2:14][CH2:15][CH3:16]

Participants

9

Reactant 5

HCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 5049666Sodium triacetoxyborohydrideHCID 58168512N-Butyl-N-(2,2-dimethoxyethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamideHCID 669633558-(2-Aminoethyl)-5-hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one hydrochloride

Product 1

HCID 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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

p-Toluenesulphonic acid monohydrate (4 molar equivalents) was added to a solution of N-butyl-N-(2,2-dimethoxyethyl)-3-(3-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanamide (limiting reagent) in THF (10 volumes) and the resulting mixture stirred for 1 hour at room temperature. The solution was then added via a peristaltic pump to a suspension of 8-(2-aminoethyl)-5-hydroxy-2H-benzo[b][1,4]oxazin-3(4H)-one hydrochloride (1 molar equivalent) and sodium bicarbonate (6.5 molar equivalents) in a mixture of NMP (4 volumes) and water (0.45 volumes) which had been stirring at room temp for 1 hour. The resulting cloudy solution was stirred for 30 mins before sodium triacetoxyborohydride (3 molar equivalents) was added portionwise and the resulting mixture was stirred for 1 hour.

Workup

  1. stirringhad been stirring at room temp for 1 hour
  2. additionwas added portionwise
  3. stirringthe resulting mixture was stirred for 1 hour

Sources & evidence

ORD record
ord-4f4f7c52e85540dc867100303454713f
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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