Diisopropylethylamine → HCID 9891133, compound

HRID 1432978Notes

Reaction equation

HRID 1432978 reaction equation
C(O[C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:17][C:18]2[CH:27]=[C:26]3[C:21]([C:22]([NH2:28])=[N:23][CH:24]=[N:25]3)=[CH:20][CH:19]=2)[C:13](=[O:29])[CH:12]1[CH2:30][O:31][CH3:32])=[O:10])C1C=CC=CC=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl:64][C:65]1[S:69][C:68]([O:70][CH2:71]C(O)=O)=[CH:67][CH:66]=1>CN(C=O)C>[NH2:28][C:22]1[C:21]2[C:26](=[CH:27][C:18]([CH2:17][N:14]3[CH2:15][CH2:16][N:11]([C:9](=[O:10])[CH2:71][O:70][C:68]4[S:69][C:65]([Cl:64])=[CH:66][CH:67]=4)[C@@H:12]([CH2:30][O:31][CH3:32])[C:13]3=[O:29])=[CH:19][CH:20]=2)[N:25]=[CH:24][N:23]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 111831442-[(5-Chlorothiophen-2-yl)oxy]acetic acidHCID 54306307HCID 54306307, compound

Product 1

HCID 9891133HCID 9891133, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(4-amino-quinazoline-7-ylmethyl)-2-methoxymethyl-3-oxo-piperazine-1-carboxylic acid benzyl ester, EXAMPLE 75, (0.69 g, 2.29 mmol) in 9 mL of DMF is added N,N-diisopropylethyl amine (0.89 g, 6.87 mmol), TBTU (0.76 g, 2.36 mmol), and 5-chloro-2-thienyloxyacetic acid, EXAMPLE 24, (0.40 g, 2.08 mmol). The solution is stirred for 16 hours. After this time the solution is concentrated. The crude material is purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA). The product fractions are lyophilized to give product as a white solid (1.0 g, 1.57 mmol). 1H NMR (d6-DMSO, 300 MHz) δ9.70 (bs, 2H), 8.78 (s, 1H), 8.29 (m, 1H), 7.55 (m, 2H), 6.72 (m, 1H), 6.22 (m, 1H), 4.80 (m, 4H), 3.78 (m, 4H), 3.59 (m, 3H), 3.31 and 3.2 (s, 3H rotational isomers).MS (ion spray) M+H=476. Elemental Analysis: C21H22ClN5O4S.1.4CF3CO2H cal: C=45.03%, H=3.68%, N=11.04%; found C=44.98%, H=3.71%, N=11.02%.

Workup

  1. concentrationAfter this time the solution is concentrated
  2. customThe crude material is purified by RP-HPLC
  3. washeluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 80% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record
ord-533ed99fd04140b7a6fcc8f107a9f847
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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