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

HRID 471259Notes

Reaction equation

HRID 471259 reaction equation
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:17][C@H:18]([OH:30])[C:19]2[C:27]3[S:26][C:25](=[O:28])[NH:24][C:23]=3[C:22]([OH:29])=[CH:21][CH:20]=2)=[CH:11][CH:10]=1)(=O)=O.FC(F)(F)C(O)=O.[CH3:45][C:46]1[S:50][C:49]([C:51]([N:53]2[CH2:58][C:57]3([CH2:63][CH2:62][NH:61][CH2:60][CH2:59]3)[O:56][CH2:55][CH2:54]2)=[O:52])=[CH:48][CH:47]=1.C(N(CC)CC)C>CC#N>[OH:30][C@H:18]([C:19]1[C:27]2[S:26][C:25](=[O:28])[NH:24][C:23]=2[C:22]([OH:29])=[CH:21][CH:20]=1)[CH2:17][N:16]([CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:7][CH2:6][N:61]2[CH2:62][CH2:63][C:57]3([O:56][CH2:55][CH2:54][N:53]([C:51]([C:49]4[S:50][C:46]([CH3:45])=[CH:47][CH:48]=4)=[O:52])[CH2:58]3)[CH2:59][CH2:60]2)=[CH:14][CH:13]=1)[C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 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 methanesulfonateHCID 67292300(5-Methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989251(R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(5-methylthiophene-2-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzyl)carbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

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) (0.426 g) in MeCN (2 mL) was added dropwise to a solution of (5-methylthiophen-2-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 9, step b) (0.154 g) and triethylamine (0.15 mL) in MeCN (5 mL) at RT under argon. The resulting mixture was stirred at 60° C. under argon for 16 h, and then at 80° C. for an additional 3 h. After cooling to RT the solvent was removed in vacuo. The residue was taken up in DCM, washed with brine and water (×2), dried over sodium sulphate, filtered and evaporated in vacuo. The brown solid was purified by silica gel chromatography eluting with 0-10% MeOH in DCM to give the subtitled compound as a yellow solid. Yield 0.246 g.

Workup

  1. waitat 80° C. for an additional 3 h
  2. temperatureAfter cooling to RT the solvent
  3. customwas removed in vacuo
  4. washwashed with brine and water (×2)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe brown solid was purified by silica gel chromatography
  9. washeluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-4c9377d66d764f24bcd69ec912d00e2b
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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