p-Toluenesulfonic acid monohydrate → HCID 58153926, compound

HRID 2234333Notes

Reaction equation

HRID 2234333 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:24])[C:7](=[O:23])[C:8]3([CH2:22]C[CH2:20][CH2:19][CH2:18]3)[CH2:9][N:10]([CH:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[C:11]=2[N:12]=1.[NH2:25][C:26]1[CH:41]=[CH:40][C:29]([C:30]([NH:32][CH:33]2[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]2)=[O:31])=[CH:28][C:27]=1[O:42][CH3:43].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)CC(O)C>[CH:13]1([N:10]2[CH2:9][C:8]3([CH2:22][CH2:20][CH2:19][CH2:18]3)[C:7](=[O:23])[N:6]([CH3:24])[C:5]3[CH:4]=[N:3][C:2]([NH:25][C:26]4[CH:41]=[CH:40][C:29]([C:30]([NH:32][CH:33]5[CH2:34][CH2:35][N:36]([CH3:39])[CH2:37][CH2:38]5)=[O:31])=[CH:28][C:27]=4[O:42][CH3:43])=[N:12][C:11]2=3)[CH2:14][CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 115290634-Amino-3-methoxy-n-(1-methylpiperidin-4-yl)benzamideHCID 86617564HCID 86617564, compound2×

Product 1

HCID 58153926HCID 58153926, compound

Reagents, catalysts & solvents 1

HCID 79104-Methyl-2-PentanolSolvent

Procedure

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclohexane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 255; 80 mg, 0.24 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 63 mg, 0.24 mmol) and p-toluenesulphonic acid monohydrate (114 mg, 0.60 mmol) were heated in 4-methyl-2-pentanol (3 mL) at 140° C. for 3 hours. The mixture was cooled and absorbed on to an SCX column, which was then washed with methanol and eluted with ammonia in methanol. Product containing fractions were evaporated and the residue purified on a silica column (2% 7N ammonia in methanol/DCM) to give the title compound as a white solid. (70 mg, 52%)

Workup

  1. temperatureThe mixture was cooled
  2. customabsorbed on to an SCX column, which
  3. washwas then washed with methanol
  4. washeluted with ammonia in methanol
  5. additionProduct containing fractions
  6. customwere evaporated
  7. customthe residue purified on a silica column (2% 7N ammonia in methanol/DCM)

Sources & evidence

ORD record
ord-15c13141c7c54f51b206746f063b0011
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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