Hydrochloric Acid → N-(4-{4-amino-7-[(1E)-3-(3-aminopyrrolidin-1-yl)prop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

HRID 2390722Notes

Reaction equation

HRID 2390722 reaction equation
[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH:34]=O)=[CH:4][N:3]=1.[NH:36]1[CH2:40][CH2:39][CH:38]([NH:41]C(=O)OC(C)(C)C)[CH2:37]1.Cl.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>CO>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:32]=[CH:33]/[CH2:34][N:36]2[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37]2)=[CH:4][N:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2757234tert-butyl N-(pyrrolidin-3-yl)carbamateHCID 18451050N-(4-{4-amino-7-[(1E)-3-oxoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide

Product 1

HCID 18450991N-(4-{4-amino-7-[(1E)-3-(3-aminopyrrolidin-1-yl)prop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamideYield 19.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

N-(4-{4-Amino-7-[(1E)-3-oxoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide (100 mg, 0.207 mmol) and tert-butyl pyrrolidin-3-ylcarbamate (115.7 mg, 0.621 mmol) were reacted according to General Procedure B. The crude product (135 mg, 0.207 mmol) was dissolved in methanol (1 mL) and treated with 6.0 M hydrochloric acid in 1,4 dioxane (0.518 mL, 2.07 mmol) and heated to 55 degrees Celsius for 4 hours. The mixture was cooled to room temperature then 1M sodium carbonate solution (5 mL) was added and product was extracted with ethyl acetate (3×10 mL). The organic layer was separated, dried over magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The product was purified via flash chromatography to furnish the title compound as an ivory powder (22.5 mg, 0.0408 mmol): LCMS (Conditions a): MH−=551 RT=3.62 minutes; 1H NMR (DMSO-d6, 400 MHz) δ 9.51 (1H), 7.97 (2H), 7.72 (1H), 7.63 (2H), 7.36 (2H), 7.21 (1H), 7.15 (1H), 7.07 (1H), 6.70 (1H), 6.26 (1H), 5.65 (1H), 4.04 (3H), 3.91 (3H), 3.51 (1H), 3.29 (2H), 2.71 (2H), 2.45 (2H), 2.10 (1H), 1.53 (1H).

Workup

  1. temperatureheated to 55 degrees Celsius for 4 hours
  2. extractionproduct was extracted with ethyl acetate (3×10 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customThe product was purified via flash chromatography

Sources & evidence

ORD record
ord-55da40b3e08b40f99574b0ed0a659249
Source dataset
uspto-grants-2012_09
Patent number
US08273736B2

Reaction notes

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