Diisopropylethylamine → 5-Chloro-N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine

HRID 1842686

Reaction equation

HRID 1842686 reaction equation
Cl.Cl.[CH3:3][N:4]([CH3:10])[C@@H:5]1[CH2:9][CH2:8][NH:7][CH2:6]1.[Cl:11][C:12]1[C:13]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:14][C:15]([NH:18][C:19]2[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[C:22](F)=[CH:21][C:20]=2[O:29][CH3:30])=[N:16][CH:17]=1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.CO>[Cl:11][C:12]1[C:13]([C:31]2[CH:32]=[N:33][N:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=23)=[N:14][C:15]([NH:18][C:19]2[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[C:22]([N:7]3[CH2:8][CH2:9][C@@H:5]([N:4]([CH3:10])[CH3:3])[CH2:6]3)=[CH:21][C:20]=2[O:29][CH3:30])=[N:16][CH:17]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 53487164(3R)-N,N-dimethylpyrrolidin-3-amine dihydrochlorideHCID 71239348HCID 71239348, compound2×

Product 1

HCID 712408395-Chloro-N-[4-[(3R)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amineYield 61%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

(3R)—N,N-Dimethylpyrrolidin-3-amine dihydrochloride (90 mg, 0.48 mmol) was added to a suspension of 5-chloro-N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 20, 200 mg, 0.48 mmol) and DIPEA (0.250 mL, 1.45 mmol) in DMA (3 mL). This mixture was heated at 140° C. in a microwave for 0.5 h. The mixture was then diluted with CH3OH and absorbed onto an SCX column, washed with CH3OH and eluted with 1:1 methanolic ammonia in CH2Cl2. Fractions containing the product were combined and concentrated in vacuo. Purification by FCC, eluting with 1.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (149 mg, 61%) as an orange foam; 1H NMR: 1.76-1.89 (1H, m), 2.14-2.25 (7H, m), 2.69-2.84 (1H, m), 3.12-3.27 (3H, m), 3.41-3.53 (1H, m), 3.89 (3H, s), 6.56 (1H, s), 7.13 (1H, td), 7.26-7.38 (1H, m), 8.06 (1H, s), 8.40-8.43 (2H, m), 8.73 (1H, s), 8.85 (1H, d), 8.95 (1H, s); m/z: ES+ MH+ 509.5.

Workup

  1. customabsorbed onto an SCX column
  2. washwashed with CH3OH
  3. washeluted with 1:1 methanolic ammonia in CH2Cl2
  4. additionFractions containing the product
  5. concentrationconcentrated in vacuo
  6. customPurification by FCC
  7. washeluting with 1.5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-e9ceb7c30279437091f0bf4f13d14f71
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Linked notes

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