4-Methyl-2-Pentanol → 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamide

HRID 2234327Notes

Reaction equation

HRID 2234327 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:6]([CH3:21])[C:7](=[O:20])[C:8]3([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.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:34][C:35]1[CH:53]=[CH:52][C:38]([C:39]([NH:41][CH2:42][C:43]([CH3:51])([CH3:50])[CH2:44][N:45]2[CH2:49][CH2:48][CH2:47][CH2:46]2)=[O:40])=[CH:37][C:36]=1[O:54][CH3:55].CC(C)CC(O)C>CO>[CH:13]1([N:10]2[CH2:9][C:8]3([CH2:19][CH2:18]3)[C:7](=[O:20])[N:6]([CH3:21])[C:5]3[CH:4]=[N:3][C:2]([NH:34][C:35]4[CH:53]=[CH:52][C:38]([C:39]([NH:41][CH2:42][C:43]([CH3:50])([CH3:51])[CH2:44][N:45]5[CH2:49][CH2:48][CH2:47][CH2:46]5)=[O:40])=[CH:37][C:36]=4[O:54][CH3:55])=[N:12][C:11]2=3)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 79104-Methyl-2-PentanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 579699392-chloro-9-cyclopentyl-8,9-dihydro-5-methylspiro[5H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclopropan]-6(7H)-one2×HCID 686858814-amino-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamide2×

Product 1

HCID 686865834-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclopropane-1,7'-pyrimido[5,4-b][1,4]diazepine]-2'-ylamino)-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamideYield 18%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

2′-chloro-9′-cyclopentyl-5′-methyl-8′,9′-dihydrospiro[cyclopropane-1,7′-pyrimido[5,4-b][1,4]diazepin]-6′(5′H)-one (Intermediate 130; 101 mg, 0.33 mmol), p-toluenesulphonic acid monohydrate (155 mg, 0.81 mmol) and 4-amino-N-(2,2-dimethyl-3-pyrrolidin-1-yl-propyl)-3-methoxy-benzamide (Intermediate 206; 100 mg, 0.33 mmol) were added to 4-methyl-2-pentanol (7 mL). The reaction was heated at 120° C. over the weekend. The sample was transferred to an SCX cartridge (10 g) pre-wet with methanol, then washed with methanol and eluted with methanolic ammonia. Product containing fractions were combined and evaporated and the resultant material purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (34 mg, 18%).

Workup

  1. washwashed with methanol
  2. washeluted with methanolic ammonia
  3. additionProduct containing fractions
  4. customevaporated
  5. customthe resultant material purified by base modified reverse phase preparative HPLC

Sources & evidence

ORD record
ord-5ce733ea894e4b388222cf00dedf8c24
Source dataset
uspto-grants-2010_05
Patent number
US07709471B2

Reaction notes

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