Sodium Carbonate → HCID 44548920, compound

HRID 1676619Notes

Reaction equation

HRID 1676619 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([F:15])([F:14])[CH2:8][N:7]([CH:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[C:6]=2[N:21]=1.[NH2:22][C:23]1[CH:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][F:38])[CH2:32][CH2:31]2)=[O:28])=[CH:25][C:24]=1[O:41][CH3:42].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(C)C.ClCCl>[CH:16]1([N:7]2[CH2:8][C:9]([F:15])([F:14])[C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:22][C:23]4[CH:40]=[CH:39][C:26]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][N:33]([CH2:36][CH2:37][F:38])[CH2:34][CH2:35]5)=[O:28])=[CH:25][C:24]=4[O:41][CH3:42])=[N:21][C:6]2=3)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 579555742-Chloro-9-cyclopentyl-7,7-difluoro-5-methyl-8,9-dihydro-5H-pyrimido[4,5-B][1,4]diazepin-6(7H)-oneHCID 580151444-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide

Product 1

HCID 44548920HCID 44548920, compoundYield 55.6%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 0.08 g (0.25 mmole) of 2-chloro-9-cyclopentyl-7,7-difluoro-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-20) and 0.075 g (0.25 mmole) of 4-amino-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide and 0.072 g (0.38 mmole) of p-toluenesulfonic acid monohydrate in 3 mL of isopropanol was stirred in a sealed tube at 140 degrees overnight. The mixture was cooled, and dichloromethane and saturated sodium carbonate were added. The mixture was extracted twice with dichloromethane. The combined organic layers were washed three times with sodium carbonate three times with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with dichloromethane-methanol (gradient, 100:0-90:10) gave 0.080 g of 4-(9-cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepin-2-ylamino)-N-[1-(2-fluoro-ethyl)-piperidin-4-yl]-3-methoxy-benzamide (I-75).

Workup

  1. temperatureThe mixture was cooled
  2. extractionThe mixture was extracted twice with dichloromethane
  3. washThe combined organic layers were washed three times with sodium carbonate three times with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography
  8. washeluting with dichloromethane-methanol (gradient, 100:0-90:10)

Sources & evidence

ORD record
ord-755e9594f2564b7fb6e7a010f88648b4
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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