Carbonate Ion → HCID 25015462, compound

HRID 2111304Notes

Reaction equation

HRID 2111304 reaction equation
FC(F)(F)C(O)=O.[CH:8]1([N:14]2[CH2:20][CH:19]([CH3:21])[C:18](=[O:22])[N:17]([CH3:23])[C:16]3[CH:24]=[N:25][C:26]([NH:28][C:29]4[CH:44]=[CH:43][C:32]([C:33]([NH:35][CH:36]5[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]5)=[O:34])=[CH:31][C:30]=4[O:45][CH3:46])=[N:27][C:15]2=3)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.C(=O)([O-])[O-]>O1CCCC1>[CH:8]1([N:14]2[CH2:20][CH:19]([CH3:21])[C:18](=[O:22])[N:17]([CH3:23])[C:16]3[CH:24]=[N:25][C:26]([NH:28][C:29]4[CH:44]=[CH:43][C:32]([C:33]([NH:35][CH:36]5[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]5)=[O:34])=[CH:31][C:30]=4[O:45][CH3:46])=[N:27][C:15]2=3)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 19660Carbonate IonHCID 68903302HCID 68903302, compound

Product 1

HCID 25015462HCID 25015462, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.050 g (0.00016 mole) of (rac)-2-chloro-9-cyclohexyl-5,7-dimethyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-19), 0.040 g (0.00016 mole) of 4-amino-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide, 0.050 g of p-toluenesulfonic acid monohydratein 4.0 mL of 2-propanol was heated at 200 degrees for 1 hour in a microwave reactor. The reaction mixture was purified by C18 reverse phase chromatography, eluting with acetonitrile—water containing 0.075% trifluoroacetic acid to give 0.066 g of (rac)-4-(9-cyclohexyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide trifluoroacetic acid salt as a white powder. To a suspension of 0.066 of (rac)-4-(9-cyclohexyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide trifluoroacetic acid salt in tetrahydrofuran was added 0.25 g of SilicaBond Carbonate (Silicycle). The mixture was stirred at room temperature for 4 hours, then filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with dichloromethane-methanol (100:0-75:25) to give 0.041 g of (rac)-4-(9-cyclohexyl-5,7-dimethyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-3-methoxy-N-(1-methyl-piperidin-4-yl)-benzamide (I-19) as a white powder. HRMS (ES+) m/z Calcd for C29H41N7O3+H [(M+H)+]: 536.3344. Found: 536.3343.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography
  4. washeluting with dichloromethane-methanol (100:0-75:25)

Sources & evidence

ORD record
ord-7a9fa5c5d5424a6ab0faa538d0e2f2bf
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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