Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamate → Methyl (6-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1h-imidazo[4,5-b]pyridin-2-yl)carbamate

HRID 241211Notes

Reaction equation

HRID 241211 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[N:15]1[CH2:21][C:20]2[CH:22]=[C:23]([C:26]3[CH:27]=[C:28]([NH2:33])[C:29]([NH2:32])=[N:30][CH:31]=3)[CH:24]=[CH:25][C:19]=2[O:18][CH2:17][CH2:16]1.[CH3:34][O:35][C:36]([NH:38][C:39](=NC(OC)=O)SC)=[O:37]>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[N:15]1[CH2:21][C:20]2[CH:22]=[C:23]([C:26]3[CH:27]=[C:28]4[NH:33][C:39]([NH:38][C:36](=[O:37])[O:35][CH3:34])=[N:32][C:29]4=[N:30][CH:31]=3)[CH:24]=[CH:25][C:19]=2[O:18][CH2:17][CH2:16]1

Participants

4

Reactant 2

HCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 668204335-{4-[6,7-Bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}pyridine-2,3-diamine

Product 1

HCID 59586209Methyl (6-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1h-imidazo[4,5-b]pyridin-2-yl)carbamateYield 55%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 5-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}pyridine-2,3-diamine (85 mg, 0.19 mmol) in acetic acid (3 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (40 mg, 0.19 mmol). The reaction mixture was heated (65° C.) for 18 h and then concentrated. The resulting residue was dissolved in acetonitrile and purified by preparative reverse phase HPLC to provide methyl (6-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1H-imidazo[4,5-b]pyridin-2-yl)carbamate (55 mg, 54% yield) as a white solid. 1H NMR (400 MHz, DMSO-D6): δ 7.93 (br, 2H), 7.93 (br, 1H), 7.78 (br, 1H), 7.59 (dd, 1h), 7.31 (s, 1H), 7.14 (dd, 1H), 7.09 (s, 1H), 6.95 (d, 1H), 4.60 (s, 2H), 4.43 (m, 2H), 3.89 (s, 3H), 3.78 (s, 3H), 3.73 (m, 2H), 3.53 (s, 3H), MS (EI) for C28H26N6O5: 527 (MH+).

Workup

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

Sources & evidence

ORD record
ord-628e39f277354c6ab01bef6c37247108
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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