Formaldehyde → 2-tert-Butyl-5-(3-(1-(hydroxymethyl)-5-(5-methyl-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one

HRID 872171Notes

Reaction equation

HRID 872171 reaction equation
[C:1]([C:5]1[S:38][C:8]2[C:9](=[O:37])[N:10]([C:12]3[C:13]([CH3:36])=[C:14]([C:18]4[CH:19]=[C:20]([NH:25][C:26]5[CH:35]=[C:29]6[CH2:30][N:31]([CH3:34])[CH2:32][CH2:33][N:28]6[N:27]=5)[C:21](=[O:24])[NH:22][N:23]=4)[CH:15]=[CH:16][CH:17]=3)[CH2:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:39]=[O:40]>CO>[C:1]([C:5]1[S:38][C:8]2[C:9](=[O:37])[N:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]4[CH:19]=[C:20]([NH:25][C:26]5[CH:35]=[C:29]6[CH2:30][N:31]([CH3:34])[CH2:32][CH2:33][N:28]6[N:27]=5)[C:21](=[O:24])[N:22]([CH2:39][OH:40])[N:23]=4)[C:13]=3[CH3:36])[CH2:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 569290576-(3-{2-tert-Butyl-6-oxo-4H,5H,6H-thieno[2,3-c]pyrrol-5-yl}-2-methylphenyl)-4-({5-methyl-4H,5H,6H,7H-pyrazolo[1,5-a]pyrazin-2-yl}amino)-2,3-dihydropyridazin-3-one

Product 1

HCID 866979422-tert-Butyl-5-(3-(1-(hydroxymethyl)-5-(5-methyl-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrazin-2-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-oneYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
60 °C

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with 101 (2.50 g, 4.72 mmol), methanol (30 mL) and a 37% solution of formaldehyde in methanol (30 mL, 100 mmol). A reflux condenser was attached to the flask, and the reaction mixture was heated at 60° C. for 3 h under nitrogen atmosphere. After this time, the mixture was stirred at room temperature for 1 h and filtered through a Buchner funnel. The filter cake was washed with methanol (3×5 mL) and dried under vacuum at 40° C. for 12 h to afford 108a in a 93% yield (2.45 g) as a white solid: mp 185-187° C.; 1H NMR (300 MHz, DMSO-d6) δ 9.33 (s, 1H), 7.79 (s, 1H), 7.47 (m, 1H), 7.39 (s, 1H), 7.38 (s, 1H), 7.14 (s, 1H), 6.77 (t, J=7.8 Hz, 1H), 5.99 (s, 1H), 5.43 (d, J=7.5 Hz, 2H), 4.78 (s, 2H), 3.97 (t, J=5.0 Hz, 2H), 3.51 (s, 2H), 2.79 (t, J=5.0 Hz, 2H), 2.35 (s, 3H), 2.13 (s, 3H), 1.41 (s, 9H); MS (ESI+) m/z 530.2 (M+H).

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
  2. customA reflux condenser was attached to the flask
  3. filtrationfiltered through a Buchner funnel
  4. washThe filter cake was washed with methanol (3×5 mL)
  5. customdried under vacuum at 40° C. for 12 h

Sources & evidence

ORD record
ord-75ff741e75c445c6a34323c7e405838a
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

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