Triethylamine → HCID 54684181, compound

HRID 1012991Notes

Reaction equation

HRID 1012991 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]3[CH:18]([N:19]([CH3:27])[C:20](=[O:26])[C:21]([N:23]([CH3:25])[CH3:24])=[O:22])[CH2:17][NH:16][CH2:15][CH2:14][N:13]3[C:28](=[O:31])[C:29]=2[OH:30])=[O:9])=[CH:4][C:3]=1[CH3:34].C(N(CC)CC)C.C(O[C:45]1(O[Si](C)(C)C)[CH2:47][CH2:46]1)C.[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[CH:45]1([N:16]2[CH2:17][CH:18]([N:19]([CH3:27])[C:20](=[O:26])[C:21]([N:23]([CH3:24])[CH3:25])=[O:22])[C:12]3=[N:11][C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:32]=[CH:33][C:2]([F:1])=[C:3]([CH3:34])[CH:4]=4)=[O:9])=[C:29]([OH:30])[C:28](=[O:31])[N:13]3[CH2:14][CH2:15]2)[CH2:47][CH2:46]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 54684192HCID 54684192, compound

Product 1

HCID 54684181HCID 54684181, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

N-(2-{[(4-fluoro-3-methylbenzyl)amino]carbonyl}-3-hydroxy-4-oxo-4,6,7,8,9,10-hexahydropyrimido[1,2-d][1,4]diazepin-10-yl)-N,N′,N′-trimethylethanediamide (prepared as described in Example 11, Step 1-7) was dissolved in methanol and treated with triethylamine (2 eq.), [(1-ethoxycyclopropyl)oxy](trimethyl)silane and acetic acid pH=5.5. To the mixture was then added NaCNBH3 (4 eq.) and reaction was refluxed overnight. After cooling to room temperature, mixture was concentrated under reduced pressure and purified by prep 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 12.67 (bs, 1H), 10.01 (bs, 1H), 7.49 (d, J=7.52 Hz, 1H), 7.45-7.40 (m, 1H), 7.21 (t, J=8.62 Hz, 1H), 5.51-5.41 (m, 2H), 4.76 (dd, J=14.6 Hz, J=6.86 Hz, 1H), 4.66 (dd, J=14.6 Hz, J=6.41 Hz, 1H), 4.27-4.00 (m, 4H), 3.51-3.36 (m, 2H), 3.27 (s, 3H), 3.19 (s, 3H), 3.17 (s, 3H), 2.46 (s, 3H), 1.37-1.31 (m, 2H), 1.19-1.10 (m, 2H); MS (ES) C25H31FN6O5 requires 514. Found: 515 (M+H+).

Workup

  1. temperaturewas refluxed overnight
  2. concentrationmixture was concentrated under reduced pressure
  3. custompurified by prep RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant)

Sources & evidence

ORD record
ord-40bca1a439594079bc27c05a2842ef8f
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

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