Hydrochloric Acid → HCID 59375001, compound

HRID 1811175Notes

Reaction equation

HRID 1811175 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-8e343616a5524f54b73d72649735c99e
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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