Hydrochloric Acid → HCID 59375001, compound

HRID 661995Notes

Reaction equation

HRID 661995 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:13][C:14]1[C:15]([CH3:42])=[C:16]([C:20]2[C:32]3[C:31]4[C:26](=[CH:27][C:28]([N:33]5[CH2:37][CH2:36][CH2:35][C:34]5=[O:38])=[CH:29][CH:30]=4)[NH:25][C:24]=3[C:23]([C:39]([NH2:41])=[O:40])=[CH:22][CH:21]=2)[CH:17]=[CH:18][CH:19]=1.Cl>C(O)(C)C>[CH3:42][C:15]1[C:14]([NH:13][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:19][CH:18]=[CH:17][C:16]=1[C:20]1[C:32]2[C:31]3[C:26](=[CH:27][C:28]([N:33]4[CH2:37][CH2:36][CH2:35][C:34]4=[O:38])=[CH:29][CH:30]=3)[NH:25][C:24]=2[C:23]([C:39]([NH2:41])=[O:40])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 9402174-chloro-6-methylquinazolineHCID 66606250HCID 66606250, compound2×

Product 1

HCID 59375001HCID 59375001, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of 4-chloro-6-methylquinazoline (prepared by the procedure used in Steps 1 and 2 of the preparation of Intermediate 32-1, 16.81 mg, 0.094 mmol) and 4-(3-amino-2-methylphenyl)-7-(2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide (Intermediate 65-1, 25 mg, 0.063 mmol) in isopropanol (0.75 mL) was treated with hydrogen chloride (4 M in 1,4-dioxane) (0.019 mL, 0.075 mmol) and heated by microwave irradiation in a sealed tube at 140° C. for 45 min. The mixture was concentrated and the residue was purified by preparative HPLC. The residue from concentration of the appropriate effluent fractions was partitioned between NaHCO3 (aq) and EtOAc, and the aqueous phase was extracted twice more with EtOAc. The combined organic phases were dried and concentrated to provide 4-(2-methyl-3-(6-methylquinazolin-4-ylamino)phenyl)-7-(2-oxopyrrolidin-1-yl)-9H-carbazole-1-carboxamide as a tan solid (7.4 mg, 20%). 1H NMR (400 MHz, methanol-d4) δ 8.43 (1H, s), 8.22 (1H, s), 7.97 (1H, d, J=7.7 Hz), 7.84 (1H, d, J=1.3 Hz), 7.67-7.77 (2H, m), 7.46-7.58 (2H, m), 7.36 (1H, dd, J=7.3, 1.5 Hz), 7.21-7.30 (2H, m), 7.13 (1H, d, J=7.9 Hz), 3.98-4.07 (2H, m), 2.65 (2H, t, J=8.1 Hz), 2.60 (3H, s), 2.18-2.28 (2H, m), 1.96 (3H, s). Mass spectrum m/z 541.5 (M+H)+.

Workup

  1. customprepared by the procedure
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by preparative HPLC
  4. customThe residue from concentration of the appropriate effluent fractions was partitioned between NaHCO3 (aq) and EtOAc
  5. extractionthe aqueous phase was extracted twice more with EtOAc
  6. customThe combined organic phases were dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-f6e56c6e3bac479ca5b58224220a230a
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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