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

HRID 471267Notes

Reaction equation

HRID 471267 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.[CH:38]([C:41]1[S:42][C:43]([C:46]([N:48]2[CH2:53][C:52]3([CH2:58][CH2:57][NH:56][CH2:55][CH2:54]3)[O:51][CH2:50][CH2:49]2)=[O:47])=[CH:44][N:45]=1)([CH3:40])[CH3:39].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:56]2[CH2:55][CH2:54][C:52]3([O:51][CH2:50][CH2:49][N:48]([C:46]([C:43]4[S:42][C:41]([CH:38]([CH3:40])[CH3:39])=[N:45][CH:44]=4)=[O:47])[CH2:53]3)[CH2:58][CH2:57]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 57989156(2-Isopropylthiazol-5-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 57989239(R)-tert-Butyl 2-hydroxy-2-(4-hydroxy-2-oxo-2,3-dihydrobenzo[d]thiazol-7-yl)ethyl(4-(2-(4-(2-isopropylthiazole-5-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

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) (0.575 g) in MeCN (3 mL) was added dropwise to a solution of (2-isopropylthiazol-5-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (example 114, step b) (0.229 g) and triethylamine (0.21 mL) in MeCN (7.3 mL) at RT under argon. The resulting mixture was stirred at 80° C. under argon for 16 h. After cooling to RT the solvent was removed in vacuo. The residue was taken up in DCM (25 mL), washed with brine (20 mL) and water (20 mL), dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by silica gel chromatography eluting with 0-8% MeOH in DCM to give the subtitled compound as a yellow solid. Yield 0.395 g.

Workup

  1. temperatureAfter cooling to RT the solvent
  2. customwas removed in vacuo
  3. washwashed with brine (20 mL) and water (20 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-8% MeOH in DCM

Sources & evidence

ORD record
ord-27ffaa4264bb415c8c18dbe5828c2df4
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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