Dimethylformamide → HCID 86592558, compound

HRID 1433065Notes

Reaction equation

HRID 1433065 reaction equation
[Cl:1][C:2]1[S:6][C:5](C(N=[N+]=[N-])=O)=[CH:4][CH:3]=1.[NH2:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([CH2:23][N:24]3[CH:29]([CH3:30])[CH2:28][NH:27][CH:26]([CH2:31][CH2:32][CH3:33])[C:25]3=[O:34])=[CH:20][CH:21]=2)[N:16]=[CH:15][N:14]=1.C[N:36]([CH:38]=[O:39])C>>[Cl:1][C:2]1[S:6][C:5]([NH:36][C:38]([N:27]2[CH2:28][C@H:29]([CH3:30])[N:24]([CH2:23][C:19]3[CH:18]=[C:17]4[C:22]([C:13]([NH2:12])=[N:14][CH:15]=[N:16]4)=[CH:21][CH:20]=3)[C:25](=[O:34])[C@@H:26]2[CH2:31][CH2:32][CH3:33])=[O:39])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 9948722HCID 9948722, compoundHCID 12330501HCID 12330501, compound

Product 1

HCID 86592558HCID 86592558, compound

Conditions

Temperature
100 °C

Procedure

A mixture of 5-chloro-thiophene-2-carbonyl azide (28 mg, 0.15 mmol, EXAMPLE 38) and 4-[4-Amino-quinazolin-7-ylmethyl]-5-methyl-3-oxo-2-propyl-piperazine, EXAMPLE 888, (26 mg, 0.08 mmol) in 3 mL of dry DMF is heated at 100° C. for 1 h. The resulting mixture is concentrated in vacuo. 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 (18 mg, 0.03 mmol) as a white solid. 1H NMR (d6-DMSO, 300 MHz) δ9.96 (bs, 1H), 9.70 (bs, 2H), 8.72 (s, 1H), 8.22 (d, 1H), 7.55 (d, 1H), 7.50 (s, 1H), 6.68 (d, 1H), 6.37 (d, 1H), 4.99-4.38 (m, 3H, rotamers), 4.15 (m, 1H, rotamers), 3.58 (m, 1H, rotamers), 3.10 (m, 1H), 1.85 (m, 2H), 1.32 (m, 2H), 1.07 (m, 3H, rotamers), 0.88 (t, 3H). ISP MS, [M+H]+=473, 475 (Cl pattern).

Workup

  1. concentrationThe resulting mixture is concentrated in vacuo
  2. customThe crude product is purified by RP-HPLC
  3. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 70% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record
ord-465773de76c944b09e5677808b448aed
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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