Triethylamine → (R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(5-methylthiophene-3-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

HRID 1689476Notes

Reaction equation

HRID 1689476 reaction equation
C(N(CC)CC)C.[CH3:8][C:9]1[S:13][CH:12]=[C:11]([C:14]([N:16]2[CH2:21][C:20]3([CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[O:19][CH2:18][CH2:17]2)=[O:15])[CH:10]=1.CS(O[CH2:32][CH2:33][O:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][N:42]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:43][C@H:44]([OH:56])[C:45]2[C:53]3[S:52][C:51](=[O:54])[NH:50][C:49]=3[C:48]([OH:55])=[CH:47][CH:46]=2)=[CH:37][CH:36]=1)(=O)=O>C(#N)C>[OH:56][C@H:44]([C:45]1[C:53]2[S:52][C:51](=[O:54])[NH:50][C:49]=2[C:48]([OH:55])=[CH:47][CH:46]=1)[CH2:43][N:42]([CH2:41][C:38]1[CH:37]=[CH:36][C:35]([O:34][CH2:33][CH2:32][N:24]2[CH2:25][CH2:26][C:20]3([O:19][CH2:18][CH2:17][N:16]([C:14]([C:11]4[CH:10]=[C:9]([CH3:8])[S:13][CH:12]=4)=[O:15])[CH2:21]3)[CH2:22][CH2:23]2)=[CH:40][CH:39]=1)[C:57](=[O:58])[O:59][C:60]([CH3:63])([CH3:61])[CH3:62]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 57988956(5-Methylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanoneHCID 57989363(R)-2-(4-((tert-butoxycarbonyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)amino)methyl)phenoxy)ethyl methanesulfonate

Product 1

HCID 57989077(R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(5-methylthiophene-3-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
80 °C

Procedure

Triethylamine (0.25 mL) was added to a solution of (5-methylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (example 104, step b) (0.195 g) in acetonitrile (2.5 mL). This solution was added to a solution of (R)-2-(4-((tert-butoxycarbonyl(2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl)amino)methyl)phenoxy)ethyl methanesulfonate (example 108, step c) (0.5 g) in acetonitrile (2.5 mL). The resulting mixture was heated at 80° C. for 48 hours. The reaction mixture was evaporated in vacuo. Purification was by silica gel chromatography eluting with 0-10% methanol in dichloromethane to give the subtitled compound as a cream solid. Yield 0.33 g.

Workup

  1. customThe reaction mixture was evaporated in vacuo
  2. customPurification
  3. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-839b67db846d43a4a4a4940a8d2cb696
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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