Triethylamine → HCID 136216271, compound

HRID 1748720Notes

Reaction equation

HRID 1748720 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[C:15]([CH3:20])=[N:16][CH:17]=[CH:18][CH:19]=1.C(N(CC)CC)C.Cl.Cl.[CH3:30][N:31]1[C:35]2[NH:36][CH2:37][CH2:38][S:39][CH:40]([CH:41]3[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]3)[C:34]=2[C:33]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=2)=[N:32]1>C1COCC1.C(OCC)(=O)C>[CH3:20][C:15]1[C:14]([NH:13][C:5]([N:44]2[CH2:45][CH2:46][CH:41]([CH:40]3[S:39][CH2:38][CH2:37][NH:36][C:35]4[N:31]([CH3:30])[N:32]=[C:33]([C:47]5[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=5)[C:34]3=4)[CH2:42][CH2:43]2)=[O:11])=[CH:19][CH:18]=[CH:17][N:16]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 5726163-Amino-2-methylpyridineHCID 136348417HCID 136348417, compound

Product 1

HCID 136216271HCID 136216271, compoundYield 116.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of triphosgene (0.017 g, 0.056 mmol) and 3-amino-2-methylpyridine (0.018 g, 0.17 mmol) in anhydrous THF (5 mL) was added dropwise triethylamine (0.14 mL, 1 mmol), at about 0° C. After stirring for about 5 min at about 0° C., 1-methyl-4-(4-piperidyl)-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepine dihydrochloride (0.07 g, 0.17 mmol, Preparation #4) was added at about 0° C. Subsequently, the mixture was stirred for about 1 h and allowed to come to rt. Then the mixture was diluted with ethyl acetate (10 mL), washed with water (10 mL) and brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (SiO2, DCM/methanol/ammonium hydroxide 92:7.5:0.5) to give N-(2-methyl-3-pyridyl)-4-[1-methyl-3-(2-pyridyl)-4,6,7,8-tetrahydropyrazolo[3,4-e][1,4]thiazepin-4-yl]piperidine-1-carboxamide (0.03 g, 0.065 mmol, 26%) as an off white solid: LC-MS (Table 1, Method b) Rt=2.00 min; m/z 464 (M+H)+.

Workup

  1. customat about 0° C
  2. stirringSubsequently, the mixture was stirred for about 1 h
  3. customto come to rt
  4. washwashed with water (10 mL) and brine (10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2, DCM/methanol/ammonium hydroxide 92:7.5:0.5)

Sources & evidence

ORD record
ord-305bbde616324737ba6a13a6160b83cc
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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