Dimethylamine → 2'-tert-butyl-1-(1-(dimethylamino)isoquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one

HRID 881013Notes

Reaction equation

HRID 881013 reaction equation
[CH3:1][NH:2][CH3:3].CO.[C:6]([N:10]1[CH:18]=[C:17]2[C:12]([C:13](=[O:37])[NH:14][C:15]3([CH2:23][CH2:22][N:21]([C:24]([C:26]4[CH:35]=[C:34]5[C:29]([CH:30]=[CH:31][N:32]=[C:33]5Cl)=[CH:28][CH:27]=4)=[O:25])[CH2:20][CH2:19]3)[CH2:16]2)=[N:11]1)([CH3:9])([CH3:8])[CH3:7]>>[C:6]([N:10]1[CH:18]=[C:17]2[C:12]([C:13](=[O:37])[NH:14][C:15]3([CH2:23][CH2:22][N:21]([C:24]([C:26]4[CH:35]=[C:34]5[C:29]([CH:30]=[CH:31][N:32]=[C:33]5[N:2]([CH3:3])[CH3:1])=[CH:28][CH:27]=4)=[O:25])[CH2:20][CH2:19]3)[CH2:16]2)=[N:11]1)([CH3:9])([CH3:8])[CH3:7]

Participants

4

Reactant 3

HCID 674DimethylamineHCID 887MethanolHCID 866646192'-tert-butyl-1-(1-chloroisoquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one

Product 1

HCID 674918062'-tert-butyl-1-(1-(dimethylamino)isoquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-oneYield 61%

Conditions

Temperature
60 °C

Procedure

A solution of dimethylamine in methanol (1.75 mL, 3.50 mmol, 2 M) was added to 2′-tert-butyl-1-(1-chloroisoquinoline-7-carbonyl)-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(2′H)-one (158 mg, 0.350 mmol). The reaction vessel was sealed and the mixture was heated to 60° C. and stirred for 65 hours. The reaction was cooled to room temperature and concentrated. Purification by flash column chromatography (1-15% methanol/dichloromethane) gave the title compound (99 mg, 61%) as a white solid. +APCI (M+H) 461.4; 1H NMR (400 MHz, CDCl3, δ): 8.16-8.20 (m, 1H), 8.12 (d, J=5.9 Hz, 1H), 7.75 (d, J=8.2 Hz, 1H), 7.58-7.64 (m, 1H), 7.37 (s, 1H), 7.14 (d, J=5.9 Hz, 1H), 6.00 (br. s., 1H), 3.40-3.71 (m, 4H), 3.10-3.28 (m, 6H), 2.85 (s, 2H), 1.64-1.99 (m, 4H), 1.60 (s, 9H).

Workup

  1. customThe reaction vessel was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated
  4. customPurification by flash column chromatography (1-15% methanol/dichloromethane)

Sources & evidence

ORD record
ord-69162bebd82c4a47a36f37809b410b50
Source dataset
uspto-grants-2015_03
Patent number
US08993586B2

Reaction notes

Loading…