Methylamine → HCID 178485543, compound

HRID 1014448Notes

Reaction equation

HRID 1014448 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:28]=[C:27]4[C:23]([CH2:24][CH2:25][N:26]4[C:29](=[O:34])[CH2:30][N:31]([CH3:33])[CH3:32])=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[CH:3]=1.[CH3:40]N>O1CCCC1>[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:5]([C:6]([NH:8][CH3:40])=[O:7])=[C:4]([NH:12][C:13]2[N:18]=[C:17]([NH:19][C:20]3[CH:28]=[C:27]4[C:23]([CH2:24][CH2:25][N:26]4[C:29](=[O:34])[CH2:30][N:31]([CH3:32])[CH3:33])=[CH:22][C:21]=3[O:35][CH3:36])[NH:16][C:15]3=[N:37][CH:38]=[CH:39][C:14]=23)[CH:3]=1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 178486485HCID 178486485, compound

Product 1

HCID 178485543HCID 178485543, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

The residue obtained from concentration of the filtrates generated from the synthesis of 4-chloro-2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluorobenzamide above were dissolved in tetrahydrofuran (10 mL) and 2.0M methyl amine in THF (5 mL) was added. The resulting solution was stirred for 12 hours and then concentrated to a residue under reduced pressure. The solids were dissolved in 1,4-dioxane (8 mL) and added to a microwave vial with 2.0N sodium hydroxide (8 mL). The mixture was maintained with rapid stirring under microwave irradiation at 120° C. for 8 minutes, cooled, poured into ethyl acetate/tetrahydrofuran/saturated sodium bicarbonate, and the organic layer was dried over sodium sulfate, taken to a residue under reduced pressure, and purified by chromatography on SiO2 to afford 4-chloro-2-[(2-{[1-(N,N-dimethylglycyl)-5-(methyloxy)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]-6-fluoro-N-methylbenzamide (0.078 g); 1H NMR (400 MHz, DMSO-d6) δ ppm 11.31 (s, 1H), 10.53 (s, 1H), 8.62 (d, J=2.57 Hz, 1H), 8.49-8.56 (m, 2H), 7.67 (s, 1H), 7.05 (dd, J=10.26, 1.83 Hz, 1H), 6.96-7.00 (m, 1H), 6.95 (s, 1H), 6.21-6.28 (m, 1H), 4.13 (t, J=8.43 Hz, 2H), 3.76 (s, 3H), 3.13 (s, 2H), 3.09 (t, J=8.62 Hz, 2H), 2.80 (d, J=4.77 Hz, 3H), 2.21 (s, 6H). ESIMS (M+H)+=567.

Workup

  1. customThe residue obtained from concentration of the filtrates
  2. concentrationconcentrated to a residue under reduced pressure
  3. dissolutionThe solids were dissolved in 1,4-dioxane (8 mL)
  4. additionadded to a microwave vial with 2.0N sodium hydroxide (8 mL)
  5. temperatureThe mixture was maintained
  6. stirringwith rapid stirring under microwave irradiation at 120° C. for 8 minutes
  7. temperaturecooled
  8. additionpoured into ethyl acetate/tetrahydrofuran/saturated sodium bicarbonate
  9. dry with materialthe organic layer was dried over sodium sulfate
  10. custompurified by chromatography on SiO2

Sources & evidence

ORD record
ord-00cc6e5b173d49ac9bfe3eacd1119034
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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