Triethylamine → N'-[8-ethyl-2-[(4-fluoro-3-methyl-phenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,9,10-tetrahydropyrimido[1,2-d][1,4]diazepin-10-yl]-N,N,N'-trimethyl-oxamide

HRID 1012999Notes

Reaction equation

HRID 1012999 reaction equation
[CH3:1][N:2]([C:4](=[O:28])[C:5]([N:7]([CH3:27])[CH:8]1[CH2:14][N:13]([CH2:15][CH3:16])[CH2:12][CH2:11][N:10]2[C:17](=[O:26])[C:18]([OH:25])=[C:19]([C:21]([O:23]C)=O)[N:20]=[C:9]12)=[O:6])[CH3:3].C(N(CC)CC)C.[F:36][C:37]1[CH:44]=[CH:43][C:40]([CH2:41][NH2:42])=[CH:39][C:38]=1[CH3:45]>CO>[CH2:15]([N:13]1[CH2:14][CH:8]([N:7]([CH3:27])[C:5](=[O:6])[C:4]([N:2]([CH3:3])[CH3:1])=[O:28])[C:9]2=[N:20][C:19]([C:21]([NH:42][CH2:41][C:40]3[CH:43]=[CH:44][C:37]([F:36])=[C:38]([CH3:45])[CH:39]=3)=[O:23])=[C:18]([OH:25])[C:17](=[O:26])[N:10]2[CH2:11][CH2:12]1)[CH3:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2774599(4-Fluoro-3-methylphenyl)methanamineHCID 67316012Methyl 10-[[(dimethylamino)(oxo)acetyl](methyl)amino]-8-ethyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepine-2-carboxylate

Product 1

HCID 54684184N'-[8-ethyl-2-[(4-fluoro-3-methyl-phenyl)methylcarbamoyl]-3-hydroxy-4-oxo-6,7,9,10-tetrahydropyrimido[1,2-d][1,4]diazepin-10-yl]-N,N,N'-trimethyl-oxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Crude methyl 10-[[(dimethylamino)(oxo)acetyl](methyl)amino]-8-ethyl-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepine-2-carboxylate was dissolved in methanol and treated with 1.2 eq. of triethylamine and 1.2 eq. of 4-fluoro-3-methylbenzylamine. The reaction mixture was refluxed overnight, then cooled to room temperature and purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant) affording desired compound as a white solid. 1H NMR (300 MHz, CD3CN) δ 12.4 (bs, 1H), 9.74 (bs, 1H), 7.26-7.16 (m, 2H), 6.96 (t, J=8.62 Hz, 1H), 5.40-5.22 (m, 2H), 4.51 (dd, J=14.6 Hz, J=6.86 Hz, 1H), 4.42 (dd, J=14.6 Hz, J=6.41 Hz, 1H), 4.18-3.92 (m, 3H), 3.78-3.73 (ms, 1H), 3.28-3.18 (m, 3H), 3.01 (s, 3H), 2.95 (s, 3H), 2.93 (s, 3H), 2.21 (s, 3H), 1.30 (t, J=5.97 Hz, 3H). MS (ES) C24H31FN6O5 requires 502. Found: 503 (M+H+).

Workup

  1. temperatureThe reaction mixture was refluxed overnight
  2. custompurified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant)

Sources & evidence

ORD record
ord-ff34373c2e3d49e6a8e02bdab8ad6837
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

Loading…