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-benzimidazol-2-yl)carbamate

HRID 241091Notes

Reaction equation

HRID 241091 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])=[CH: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:31]=[CH:30][C:29]4[N:32]=[C:39]([NH:38][C:36](=[O:37])[O:35][CH3:34])[NH:33][C:28]=4[CH:27]=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 66820407HCID 66820407, compound

Product 1

HCID 70211604Methyl (6-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-1h-benzimidazol-2-yl)carbamateYield 35.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 4-{-4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}-2-nitroaniline (56 mg, 0.12 mmol) in methanol (20 mL) was hydrogenated at 30 psi over 10% Pd—C (25 mg) for 4 h. The catalyst was filtered off, and the filtrate was concentrated to give 4-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}benzene-1,2-diamine (40 mg, 77% yield) as a brown oil. MS (EI) for C26H26N4O3: 443 (MH STEP 5: To a solution of 4-{4-[6,7-bis(methyloxy)quinolin-4-yl]-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl}benzene-1,2-diamine (40 mg, 0.09 mmol) in acetic acid (2 mL) was added 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (19 mg, 0.09 mmol) and the reaction mixture was stirred at 80° C. for 30 min. After cooling to room temperature the mixture was concentrated, 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-benzimidazol-2-yl)carbamate (17 mg, 25% yield) as a brown solid. 1H NMR (400 MHz, CD3OD): 8.30 (d, 1H), 7.78 (m, 2H), 7.68 (m, 2H), 7.60 (m, 1H), 7.27 (d, 2H), 7.11 (d, 1H), 7.04 (d, 1H), 5.17 (s, 2H), 4.64 (m, 2H), 4.25 (m, 2H), 4.01 (s, 3H), 3.96 (s 3H), 3.63 (s, 3H); MS (EI) for C29H27N5O5: 526 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated
  3. custompurified by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-11e0de2f7b7041bd8a0a1ce473ed6573
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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