Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamate → methyl[6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate

HRID 241194Notes

Reaction equation

HRID 241194 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]([NH2:34])[C:30]([NH2:33])=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:4][CH:3]=1.[CH3:35][O:36][C:37]([NH:39][C:40](=NC(OC)=O)SC)=[O:38]>C(O)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[C:10]([N:16]3[CH2:22][C:21]4[CH:23]=[C:24]([C:27]5[CH:28]=[C:29]6[NH:34][C:40]([NH:39][C:37](=[O:38])[O:36][CH3:35])=[N:33][C:30]6=[N:31][CH:32]=5)[CH:25]=[CH:26][C:20]=4[O:19][CH2:18][CH2:17]3)=[N:11][CH:12]=[N:13][C:14]=2[CH3:15])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 668206925-(4-{5-[(4-Fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)pyridine-2,3-diamine

Product 1

HCID 59586590methyl[6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamateYield 4.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)pyridine-2,3-diamine (0.21 g, 0.45 mmol) in acetic acid (5 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (0.09 g, 0.45 mmol). The reaction mixture was heated (60° C.) for 12 h and then concentrated. The resulting residue was dissolved in acetonitrile and purified by preparative reverse phase HPLC to provide methyl [6-(4-{5-[(4-fluorophenyl)methyl]-6-methylpyrimidin-4-yl}-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl)-1H-imidazo[4,5-b]pyridin-2-yl]carbamate (0.01 g, 4% yield) as a white solid. 1H NMR (400 MHz, DMSO-D6): δ 11.97 (bs, 1H), 8.51 (d, 1H), 8.28 (s, 1H), 7.79 (s, 1h), 7.42-7.50 (m, 1H), 6.95-7.13 (m, 6H), 4.53 (s, 2H), 4.25-4.32 (m, 2H), 4.00 (s, 2H), 3.74-3.84 (m, 5H), 2.16 (s; 3H); MS (EI) for C29H26FN7O3: 540 (MH+).

Workup

  1. concentrationconcentrated
  2. dissolutionThe resulting residue was dissolved in acetonitrile
  3. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-be49a2fa5a7d41a8aca1e309df826ac0
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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