Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamate → Methyl {6-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-1h-imidazo[4,5-b]pyridin-2-yl}carbamate

HRID 241227Notes

Reaction equation

HRID 241227 reaction equation
[CH3:1][C:2]1([CH3:31])[CH2:11][CH2:10][C:9]2[N:8]=[CH:7][N:6]=[C:5]([N:12]3[CH2:18][C:17]4[CH:19]=[C:20]([C:23]5[CH:24]=[C:25]([NH2:30])[C:26]([NH2:29])=[N:27][CH:28]=5)[CH:21]=[CH:22][C:16]=4[O:15][CH2:14][CH2:13]3)[C:4]=2[CH2:3]1.[CH3:32][O:33][C:34]([NH:36][C:37](=NC(OC)=O)SC)=[O:35]>C(O)(=O)C>[CH3:1][C:2]1([CH3:31])[CH2:11][CH2:10][C:9]2[N:8]=[CH:7][N:6]=[C:5]([N:12]3[CH2:18][C:17]4[CH:19]=[C:20]([C:23]5[CH:24]=[C:25]6[NH:30][C:37]([NH:36][C:34](=[O:35])[O:33][CH3:32])=[N:29][C:26]6=[N:27][CH:28]=5)[CH:21]=[CH:22][C:16]=4[O:15][CH2:14][CH2:13]3)[C:4]=2[CH2:3]1

Participants

4

Reactant 2

HCID 98708Methyl [[(methoxycarbonyl)amino](methylthio)methylene]carbamateHCID 668201845-[4-(6,6-Dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]pyridine-2,3-diamine

Product 1

HCID 57388833Methyl {6-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]-1h-imidazo[4,5-b]pyridin-2-yl}carbamateYield 51%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-[4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]pyridine-2,3-diamine (174 mg, 0.42 mmol) and 1,3-bis(methoxycarbonyl)-2-methyl-2-thiopseudourea (86 mg, 0.42 mmol) in acetic acid (5 mL) was stirred at 80° C. for 10 h. After cooling to room temperature the mixture was concentrated, methanol (10 mL) was added, the precipitate was filtered off, and lyophilized from a mixture of acetonitrile (2 mL), water (6 mL), and 1N hydrochloric acid (0.25 mL) to give the hydrochloride salt of the title Compound (107 mg, 48% yield) as a yellow solid. 1H NMR (400 MHz, methanol-d4): 8.53 (m, 2H), 8.35 (s, 1H), 7.78 (s, 1H), 7.58 (d, 1H), 7.10 (d, 1H), 5.18 (s, 2H), 4.49 (m, 2H), 4.34 (m, 2H), 3.93 (s, 3H), 2.86 (m, 2H), 2.61 (s, 2H), 1.71 (m, 2H), 0.95 (s, 6H); MS (EI) for C27H29N7O3: 500 (MH+).

Workup

  1. temperatureAfter cooling to room temperature the mixture
  2. concentrationwas concentrated
  3. additionmethanol (10 mL) was added
  4. filtrationthe precipitate was filtered off
  5. additionlyophilized from a mixture of acetonitrile (2 mL), water (6 mL), and 1N hydrochloric acid (0.25 mL)

Sources & evidence

ORD record
ord-d1a03b55ee1d4cd5b432521ca6336bf6
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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