Triethylamine → HCID 178428671, compound

HRID 473864Notes

Reaction equation

HRID 473864 reaction equation
[C:1]1([CH2:7][NH:8][C:9]2[NH:13][N:12]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]4[O:23][CH2:22][CH2:21][N:20]([C:24](OC(C)(C)C)=[O:25])[CH2:19][C:18]=4[CH:31]=3)[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[CH3:39][CH:40]1[CH2:45][CH2:44][N:43](C(Cl)=O)[CH2:42][CH2:41]1>C(#N)C.Cl.O1CCOCC1.CO>[CH3:39][CH:40]1[CH2:45][CH2:44][N:43]([C:24]([N:20]2[CH2:19][C:18]3[CH:31]=[C:14]([C:11]4[CH:10]=[C:9]([NH:8][CH2:7][C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[NH:13][N:12]=4)[CH:15]=[CH:16][C:17]=3[O:23][CH2:22][CH2:21]2)=[O:25])[CH2:42][CH2:41]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 152215164-Methylpiperidine-1-carbonyl ChlorideHCID 178452409HCID 178452409, compound

Product 1

HCID 178428671HCID 178428671, compoundYield 57.1%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

STEP 6 A mixture of 1,1-dimethylethyl 7-{5-[(phenylmethyl)amino]-1H-pyrazol-3-yl}-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (92 mg, 0.22 mmol) in acetonitrile (2 mL) and 4 M hydrogen chloride in 1,4-dioxane (2 mL) was stirred at 70° C. for 10 minutes. The reaction mixture was allowed to cool then concentrated and the residue suspended in N,N-dimethylformamide (2 mL). Triethylamine (123 mg, 1.21 mmol), then 4-methylpiperidine-1-carbonyl chloride (reagent preparation 37) (35 mg, 0.22 mmol) were added and the resulting mixture was stirred at room temperature for 18 hours. The crude mixture diluted with methanol (6 mL) and purified by preparative reverse phase HPLC to give 3-{4-[(4-methylpiperidin-1-yl)carbonyl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-N-(phenylmethyl)-1H-pyrazol-5-amine (56 mg, 57% yield), (400 MHz, methanol-d4): 7.49 (br, 1H), 7.45 (dd, 1H), 7.39 (d, 2H), 7.30 (t, 2H), 7.22 (dd, 1H), 6.96 (d, 1H), 5.81 (s, 1H), 4.43 (s, 2H), 4.33 (s, 2H), 4.17 (m, 2H), 3.66 to 3.59 (m, 4H), 2.80 (t, 2H), 1.67 to 1.50 (m, 3H), 1.24 to 1.12 (m, 2H), 0.96 (d, 3H); MS (EI) for C26H31N5O2: 446 (MH+).

Workup

  1. temperatureto cool
  2. concentrationthen concentrated
  3. stirringthe resulting mixture was stirred at room temperature for 18 hours
  4. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-4763b51bea2241b581662a5b61bebe24
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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