p-Toluenesulfonic acid monohydrate → HCID 68685529, compound

HRID 2234345Notes

Reaction equation

HRID 2234345 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:13][C:14]1[C:32]([F:33])=[CH:31][C:17]([C:18]([NH:20][CH:21]2[CH2:28][C@H:27]3[N:29]([CH3:30])[C@H:23]([CH2:24][CH2:25][CH2:26]3)[CH2:22]2)=[O:19])=[C:16]([F:34])[CH:15]=1.Cl[C:36]1[N:46]=[C:45]2[C:39]([N:40]([CH3:53])[C:41](=[O:52])[CH2:42][CH2:43][N:44]2[CH:47]2[CH2:51][CH2:50][CH2:49][CH2:48]2)=[CH:38][N:37]=1>CC(C)CC(O)C>[CH:47]1([N:44]2[CH2:43][CH2:42][C:41](=[O:52])[N:40]([CH3:53])[C:39]3[C:45]2=[N:46][C:36]([NH:13][C:14]2[C:32]([F:33])=[CH:31][C:17]([C:18]([NH:20][CH:21]4[CH2:28][C@H:27]5[N:29]([CH3:30])[C@H:23]([CH2:24][CH2:25][CH2:26]5)[CH2:22]4)=[O:19])=[C:16]([F:34])[CH:15]=2)=[N:37][CH:38]=3)[CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 579405262-Chloro-9-cyclopentyl-5-methyl-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one2×HCID 68685990HCID 68685990, compound2×

Product 1

HCID 68685529HCID 68685529, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Conditions

Temperature
150 °C

Procedure

p-Toluenesulphonic acid monohydrate (338 mg, 1.78 mmol) was added to 4-amino-2,5-difluoro-N-[(1S,5R)-9-methyl-9-azabicyclo[3.3.1]non-7-yl]benzamide (Intermediate 274; 220 mg, 0.71 mmol), and 2-chloro-9-cyclopentyl-5-methyl-8,9-dihydro-5H-pyrimido[5,4-b][1,4]diazepin-6(7H)-one (Intermediate 1; 200 mg, 0.71 mmol) in 4-methyl-2-pentanol (4 mL) at 25° C. The resulting mixture was heated by microwave irradiation at 150° C. for 1 hour. The crude product was purified by ion exchange chromatography, using an SCX-3 (5 g) column. The desired product was eluted from the column using 2M NH3/MeOH and product-containing fractions were evaporated to dryness. The residue was further purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (91 mg, 23.%).

Workup

  1. customThe crude product was purified by ion exchange chromatography
  2. washThe desired product was eluted from the column
  3. additionproduct-containing fractions
  4. customwere evaporated to dryness
  5. customThe residue was further purified by base modified reverse phase preparative HPLC

Sources & evidence

ORD record
ord-cff955e01cf74d60ac99e399f915eac3
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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