Diisopropylethylamine → HCID 69028744, compound

HRID 1433061Notes

Reaction equation

HRID 1433061 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][NH:16][C@@H:15]([CH2:19][O:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[C:23]([C:25]1[CH:26]=[C:27]([CH:33]=[CH:34][CH:35]=1)[CH:28]=[CH:29][C:30](O)=[O:31])#[N:24].C(N(CC)C(C)C)(C)C.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:30](=[O:31])[CH:29]=[CH:28][C:27]4[CH:26]=[C:25]([CH:35]=[CH:34][CH:33]=4)[C:23]#[N:24])[C@@H:15]([CH2:19][O:20][CH3:21])[C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 447258693-(3-Cyanophenyl)-2-propenoic acidHCID 53870984HCID 53870984, compound

Product 1

HCID 69028744HCID 69028744, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-amino-quinazoline-7-ylmethyl)-3-(S)-methoxymethyl-piperazine-2-one, EXAMPLE 75, (50 mg, 0.16 mmol) and 3-cyanocinnamic acid (29 mg, 0.17 mmol, prepared from 3-cyanobenzaldehyde) in 1 mL of DMF is added N,N-diisopropylethylamine (0.07 mL, 0.38 mmol), followed by 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) (59 mg, 0.18 mmol). The resulting mixture is stirred at room temperature for 16 h and the solution is concentrated. The crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) over 30 min and the appropriate product fractions are combined and lyopholized to provide the title compound (73 mg, 0.13 mmol) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ9.72 (bs, 2H), 8.78 (s, 1H), 8.40 (s, 1H), 8.35 (d, 1H), 8.04 (m, 1H), 7.83 (d, 1H), 7.60 (m, 4H), 7.46 (d, 1H), 5.25-4.44 (m, 4H, rotamers), 4.02 (m, 1H), 3.66 (m, 1H), 3.51-3.40 (m, 3H), 3.27 (s, 3H). ISP MS, [M+H]+=457.

Workup

  1. concentrationthe solution is concentrated
  2. customThe crude product is purified by RP-HPLC
  3. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) over 30 min

Sources & evidence

ORD record
ord-3dd0b3b197184c7b9ce3098cf4c78a28
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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