Triethylamine → HCID 118159936, compound

HRID 628400Notes

Reaction equation

HRID 628400 reaction equation
C(N(CC)CC)C.CS(Cl)(=O)=O.[Cl:13][C:14]1[CH:15]=[C:16]([CH2:39]O)[CH:17]=[C:18]([CH2:20][N:21]2[C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:30]([CH3:33])=[N:31][N:32]=4)[C:24]=3[CH:23]=[C:22]2[C:34]2[O:35][CH:36]=[N:37][N:38]=2)[CH:19]=1.Cl.[NH:42]1[CH2:45][CH:44]([OH:46])[CH2:43]1.S([O-])(=O)(=O)C>C(Cl)Cl.C1COCC1>[Cl:13][C:14]1[CH:15]=[C:16]([CH:17]=[C:18]([CH2:20][N:21]2[C:25]3[CH:26]=[CH:27][C:28]4[N:29]([C:30]([CH3:33])=[N:31][N:32]=4)[C:24]=3[CH:23]=[C:22]2[C:34]2[O:35][CH:36]=[N:37][N:38]=2)[CH:19]=1)[CH2:39][N:42]1[CH2:45][CH:44]([OH:46])[CH2:43]1

Participants

8

Reactant 5

HCID 8471Triethylamine4×HCID 31297Methanesulfonyl chloride2×HCID 85257MethanesulfonateHCID 27592903-Hydroxyazetidine hydrochloride2×HCID 118159694HCID 118159694, compound

Product 1

HCID 118159936HCID 118159936, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (49 μL, 0.35 mmol) and methanesulfonyl chloride (22 μL, 0.28 mmol, Aldrich) were added to a mixture of (3-chloro-5-{[1-methyl-7-(1,3,4-oxadiazol-2-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-c]pyridin-6-yl]methyl}phenyl)methanol (0.033 g, 0.084 mmol, from Step 4) in DCM (4.9 mL). After 30 minutes, additional triethylamine (49 μL, 0.35 mmol) and methanesulfonyl chloride (22 μL, 0.28 mmol) were added. After 30 additional minutes, the mixture was briefly heated to reflux and then cooled. The solvent was removed in vacuo. The crude mesylate was reconstituted in THF (1.9 mL) and Methanol (1.9 mL). Half of this solution was added to azetidin-3-ol hydrochloride (37 mg, 0.33 mmol, Aldrich) and triethylamine (46 μL, 0.33 mmol) in THF (0.2 mL). [The other half of the mesylate solution was used in Example 140]. After 20 minutes, additional azetidin-3-ol hydrochloride (125 mg, 1.12 mmol, Aldrich) and triethylamine (156 μL, 1.12 mmol) were added and the mixture was stirred overnight. Sequential preparative HPLC-MS runs were used to purify the product (Waters SunFire C18, eluting with a gradient of MeCN/H2O containing 0.1% TFA, followed by Waters XBridge C18, eluting with a gradient of MeCN/H2O containing 0.15% NH4OH). Yield: (5 mg, 10%).

Workup

  1. temperatureAfter 30 additional minutes, the mixture was briefly heated
  2. temperatureto reflux
  3. temperaturecooled
  4. customThe solvent was removed in vacuo
  5. waitAfter 20 minutes
  6. customto purify the product (Waters SunFire C18
  7. washeluting with a gradient of MeCN/H2O containing 0.1% TFA
  8. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-9a238be1613441009203fa23cb7d4ceb
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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