Ammonium Hydroxide → HCID 59441759, compound

HRID 1014529Notes

Reaction equation

HRID 1014529 reaction equation
Cl.Cl[C:3]1[N:16]2[C:7](=[N:8][C:9]3[C:14]([C:15]2=[O:17])=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:6]2[CH:18]=[CH:19][N:20]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[C:5]=2[N:4]=1.[CH3:31][N:32]([CH2:34][C:35]([N:37]1[C:45]2[C:40](=[CH:41][C:42]([O:47][CH3:48])=[C:43]([NH2:46])[CH:44]=2)[CH2:39][CH2:38]1)=[O:36])[CH3:33].[NH4+:49].[OH-]>C1COCC1.CCOC(C)=O>[CH3:33][N:32]([CH3:31])[CH2:34][C:35]([N:37]1[C:45]2[C:40](=[CH:41][C:42]([O:47][CH3:48])=[C:43]([NH:46][C:3]3[N:16]=[C:7]([NH:8][C:9]4[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=4[C:15]([NH2:49])=[O:17])[C:6]4[CH:18]=[CH:19][N:20]([S:21]([C:24]5[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=5)(=[O:23])=[O:22])[C:5]=4[N:4]=3)[CH:44]=2)[CH2:39][CH2:38]1)=[O:36]

Participants

6

Reactant 3

HCID 14923Ammonium HydroxideHCID 25150091HCID 25150091, compoundHCID 534147641-(6-Amino-5-methoxy-2,3-dihydro-1H-indol-1-yl)-2-(dimethylamino)ethan-1-one2×

Product 1

HCID 59441759HCID 59441759, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-chloro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (500 mg, 1.084 mmol) and 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (270 mg, 1.084 mmol) in THF (50 mL) was heated at 80° C. for 7.5 h. More 1-[(dimethylamino)acetyl]-5-(methyloxy)-2,3-dihydro-1H-indol-6-amine (270 mg, 1.084 mmol) was added and the reaction mixture was heated at 80° C. for 1 h. The resulting mixture was diluted to a total of 70 mL of which 40 mL was diluted with a 27% aqueous NH4OH solution (100 mL), maintained at rt for 3 days, and diluted with EtOAc (200 mL) and washed with a saturated NaCl solution (4×125 mL). The organic layer was concentrated onto Celite and purified by silica gel chromatography using 1-10% MeOH (containing 0.2% NH3)/CH2Cl2, followed by trituration using a mixture of CH2Cl2 and Et2O to obtain 2-({2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide as a white solid (101 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.24 (s, 6H), 2.35 (s, 3H), 3.14-3.28 (m, 4H), 3.74 (s, 3H), 4.24 (t, J=8.33 Hz, 2H), 6.47 (d, J=3.85 Hz, 1H), 6.91-7.03 (m, 1H), 7.08 (s, 1H), 7.24 (t, J=7.60 Hz, 1H), 7.29-7.42 (m, 3H), 7.70-7.87 (m, 2H), 7.98 (d, J=8.24 Hz, 2H), 8.23 (s, 1H), 8.31 (br s, 1H), 8.37 (s, 1H), 8.70 (d, J=8.42 Hz, 1H), 12.22 (s, 1H); ESIMS (M+H)+=655.37.

Workup

  1. temperaturethe reaction mixture was heated at 80° C. for 1 h
  2. additionThe resulting mixture was diluted to a total of 70 mL of which 40 mL
  3. temperaturemaintained at rt for 3 days
  4. washwashed with a saturated NaCl solution (4×125 mL)
  5. concentrationThe organic layer was concentrated onto Celite
  6. custompurified by silica gel chromatography
  7. additiona mixture of CH2Cl2 and Et2O

Sources & evidence

ORD record
ord-1ca98b9ba18641f88b7b5f648c8b7ca6
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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