Methanamine, hydrochloride (1:1) → HCID 68355368, compound

HRID 1498441Notes

Reaction equation

HRID 1498441 reaction equation
ClC1C=CC2[C:6]3[N:7](C=C(I)N=3)CCOC=2N=1.Cl[C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[N:23]([CH:29]=[C:30]([C:32]4[N:36]([CH:37]([CH3:39])[CH3:38])[N:35]=[CH:34][N:33]=4)[N:31]=3)[CH2:24][CH2:25][O:26][C:27]=2[N:28]=1.[Cl-].C[NH3+].C(N(CC)C(C)C)(C)C>CN1CCCC1=O>[CH:37]([N:36]1[C:32]([C:30]2[N:31]=[C:22]3[C:21]4[CH:20]=[CH:19][C:18]([NH:7][CH3:6])=[N:28][C:27]=4[O:26][CH2:25][CH2:24][N:23]3[CH:29]=2)=[N:33][CH:34]=[N:35]1)([CH3:39])[CH3:38]

Participants

6

Reactant 4

HCID 11637Methanamine, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 58204662HCID 58204662, compound2×HCID 58204828HCID 58204828, compound

Product 1

HCID 68355368HCID 68355368, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Following the procedures of Examples herein, including Examples 20-22, 9-chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,2-f][1,4]oxazepine was converted to 9-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,2-f][1,4]oxazepine. A mixture of 110 mg (0.33 mmol) of 9-chloro-2-(1-isopropyl-1H-1,2,4-triazol-5-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,2-f][1,4]oxazepine, 87 mg (1.3 mmol) of methylammonium chloride and 0.23 ml (1.3 mmol) of N,N-diisopropylethylamine in 3.0 ml of N-methylpyrrolidinone was microwaved for 90 min at 170° C. NMP was removed under high vacuum, the residue was basified with 1 M Na2CO3 and partitioned between ethyl acetate and water. The organic extracts were washed with 5% aqueous citric acid, water, brine, dried over MgSO4 and concentrated. The residue was purified by RP HPLC (acetonitrile gradient) to give 367. Yield 12 mg. M/z 326.3, calc. 325.17. 1H NMR (400 MHz, DMSO) δ 8.37 (d, J=8.6, 1H), 7.88 (s, 1H), 7.77 (s, 1H), 6.96 (s, 1H), 6.34 (d, J=8.6, 1H), 5.88 (dt, J=13.0, 6.5, 1H), 4.46 (d, J=9.2, 4H), 2.78 (d, J=2.9, 3H), 1.46 (d, J=6.6, 6H)

Workup

  1. customwas microwaved for 90 min at 170° C
  2. customNMP was removed under high vacuum
  3. custompartitioned between ethyl acetate and water
  4. washThe organic extracts were washed with 5% aqueous citric acid, water, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified by RP HPLC (acetonitrile gradient)

Sources & evidence

ORD record
ord-7f1093bedbfe451cab4e14eaa887257f
Source dataset
uspto-grants-2015_12
Patent number
US09198918B2

Reaction notes

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