4-Chlorophenyl Isocyanate → HCID 86592557, compound

HRID 1433064Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH:18]([CH3:19])[CH2:17][NH:16][CH:15]([CH2:20][CH2:21][CH3:22])[C:14]3=[O:23])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]=[C:32]=[O:33])=[CH:27][CH:26]=1>CN(C=O)C>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]([N:16]2[CH2:17][C@H:18]([CH3:19])[N:13]([CH2:12][C:8]3[CH:7]=[C:6]4[C:11]([C:2]([NH2:1])=[N:3][CH:4]=[N:5]4)=[CH:10][CH:9]=3)[C:14](=[O:23])[C@@H:15]2[CH2:20][CH2:21][CH3:22])=[O:33])=[CH:27][CH:26]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 4-[4-Amino-quinazolin-7-ylmethyl]-5-methyl-3-oxo-2-propyl-piperazine (12 mg, 0.04 mmol, EXAMPLE 888) in 2 mL of DMF is added 4-chlorophenyl isocyanate (9 mg, 0.06 mmol). After stirring at 100° C. for 1 h, the solution is concentrated. The crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are combined and lyophilized to provide the title compound (16 mg, 0.03 mmol) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ9.74 (bs, 2H), 8.77 (m, 2H), 8.35 (m, 1H), 7.56 (m, 2H), 7.46 (d, 2H), 7.21 (d, 2H), 5.00-4.38 (m, 3H, rotamers), 4.20 (m, 1H, rotamers), 3.58 (m, 1H, rotamers), 3.10 (m, 1H), 1.86 (m, 2H), 1.33 (m, 2H), 1.08 (m, 3H, rotamers), 0.90 (t, 3H). ISP MS, [M+H]+=467, 469 (Cl pattern).

Workup

concentrationthe solution is concentrated
customThe crude product is purified by RP-HPLC
washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record: ord-c35b9c95d74a4843b3cd63326233f4bf
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612075B2

Reaction notes

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