Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamate → 1,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-imidazo[4,5-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

HRID 473885Notes

Reaction equation

HRID 473885 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][C:13]=3[CH:26]=2)[CH:5]=[N:6][C:7]=1[NH2:8].[CH3:27][O:28][C:29]([NH:31][C:32](=NC(OC)=O)SC)=[O:30]>C(O)(=O)C>[CH3:27][O:28][C:29]([NH:31][C:32]1[NH:1][C:2]2[C:7]([N:8]=1)=[N:6][CH:5]=[C:4]([C:9]1[CH:10]=[CH:11][C:12]3[O:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:14][C:13]=3[CH:26]=1)[CH:3]=2)=[O:30]

Participants

4

Reactant 2

HCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 668202021,1-dimethylethyl 7-(5,6-diaminopyridin-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate

Product 1

HCID 668202411,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-imidazo[4,5-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylateYield 84.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 1,1-dimethylethyl 7-(5,6-diaminopyridin-3-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.51 g, 1.4 mmol) in acetic acid (5 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (0.3 g, 1.4 mmol). The reaction mixture was heated 65° C. for 18 h and then concentrated. The resulting residue was suspended in water and basified with portion wise addition of solid sodium bicarbonate. After complete neutralization of the aqueous mixture the insoluble solid was collected by filtration and washed with water then 50% ethyl acetate in hexanes and the filter cake dried to give 1,1-dimethylethyl 7-(2-{[(methyloxy)carbonyl]amino}-1H-imidazo[4,5-b]pyridin-6-yl)-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (0.52 g, 83% yield), MS (EI) for C22H25N5O5: 440 (MH+).

Workup

  1. concentrationconcentrated
  2. additionThe resulting residue was suspended in water and basified with portion wise addition of solid sodium bicarbonate
  3. filtrationAfter complete neutralization of the aqueous mixture the insoluble solid was collected by filtration
  4. washwashed with water
  5. dry with material50% ethyl acetate in hexanes and the filter cake dried

Sources & evidence

ORD record
ord-5fe183211a874569a36d6ace25cbcc3b
Source dataset
uspto-grants-2014_01
Patent number
US08637499B2

Reaction notes

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