Hydrochloric Acid → HCID 66829374, compound

HRID 1686926Notes

Reaction equation

HRID 1686926 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH:15]2[CH2:16][CH2:17][CH:7]1[C:8]1[CH:9]=[C:10]([NH2:18])[CH:11]=[CH:12][C:13]=1[CH2:14]2)=[O:5])[CH3:2].Cl[C:20]1[N:25]=[C:24]([NH:26][C:27]2[CH:36]=[CH:35][CH:34]=[CH:33][C:28]=2[C:29]([NH:31][CH3:32])=[O:30])[C:23]([Cl:37])=[CH:22][N:21]=1.Cl.C([O-])(O)=O.[Na+]>C(O)(C)C>[CH2:1]([O:3][C:4]([N:6]1[CH:15]2[CH2:16][CH2:17][CH:7]1[C:8]1[CH:9]=[C:10]([NH:18][C:20]3[N:25]=[C:24]([NH:26][C:27]4[CH:36]=[CH:35][CH:34]=[CH:33][C:28]=4[C:29](=[O:30])[NH:31][CH3:32])[C:23]([Cl:37])=[CH:22][N:21]=3)[CH:11]=[CH:12][C:13]=1[CH2:14]2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 14040087HCID 14040087, compoundHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

Product 1

HCID 66829374HCID 66829374, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
140 °C

Procedure

4-Amino-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester (J. Med. Chem. 1988, 31, 433-444)(30 mg, 0.12 mmol) and 2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (36 mg, 0.12 mmol) were combined with 4 N HCl (0.030 mL, 0.12 mmol) in isopropanol (1 mL). The resulting mixture was heated in a microwave at 140° C. for 30 min. The resulting mixture was then made basic with saturated aqueous NaHCO3, extracted with CH2Cl2 (2×5 mL), dried over MgSO4, filtered, and concentrated. The resulting residue was purified with silica gel chromatography (0-100% EtOAc in hexanes) to obtain 4-[5-Chloro-4-(2-methylcarbamoyl-phenylamino)-pyrimidin-2-ylamino]-12-aza-tricyclo[7.2.1.0*2,7*]dodeca-2(7),3,5-triene-12-carboxylic acid ethyl ester as a yellow solid (30 mg, 49%). 1HNMR (400 MHz, DMSO-d6) δ 11.6 (s, 1H), 9.4 (s, 1H), 8.8 (d, 1H, J=4.6 Hz), 8.7 (d, 1H, J=8.1 Hz), 8.2 (s, 1H), 7.8 (d, 1H, J=7.1 Hz), 7.7-7.5 (m, 2H), 7.4 (m, 1H), 7.1 (t, 1H, J=7.1 Hz), 7.0 (d, 1H, J=8.3 Hz), 4.7 (m, 1H), 4.4 (m, 1H), 4.1-3.9 (m, 2H), 3.2 (d, 1H, J=14.1H), 2.8 (d, 3H, J=4.6 Hz), 2.2-2.0 (m, 2H), 1.7 (t, 1H, J=9.4 Hz), 1.6 (m, 1H), 1.2 (m, 1H), 1.2-1.0 (m, 3H); MS (m/e) 507 (M+1); mp 140-144° C.

Workup

  1. extractionextracted with CH2Cl2 (2×5 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified with silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-16c0199344fa4575a02b12f7a4295998
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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