Hydrochloric Acid → HCID 57900151, compound

HRID 627953Notes

Reaction equation

HRID 627953 reaction equation
Cl.ClC1C=CC=C[C:4]=1[N:9]1C=NN=[C:10]1C1SC2C3C=CC(N)=CC=3OCCC=2C=1.CCN(C(C)C)C(C)C.ClCC(Cl)=O.Cl[CH2:44][C:45]([NH:47][C:48]1[CH:49]=[CH:50][C:51]2[C:57]3[S:58][C:59]([C:61]4[N:65]([C:66]5[CH:71]=[CH:70][CH:69]=[CH:68][C:67]=5[Cl:72])[CH:64]=[N:63][N:62]=4)=[CH:60][C:56]=3[CH2:55][CH2:54][O:53][C:52]=2[CH:73]=1)=[O:46].Cl.N(C)C.CCN(CC)CC>C(Cl)Cl>[Cl:72][C:67]1[CH:68]=[CH:69][CH:70]=[CH:71][C:66]=1[N:65]1[CH:64]=[N:63][N:62]=[C:61]1[C:59]1[S:58][C:57]2[C:51]3[CH:50]=[CH:49][C:48]([NH:47][C:45](=[O:46])[CH2:44][N:9]([CH3:10])[CH3:4])=[CH:73][C:52]=3[O:53][CH2:54][CH2:55][C:56]=2[CH:60]=1

Participants

9

Reactant 7

HCID 313Hydrochloric AcidHCID 674DimethylamineHCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 81531DiisopropylethylamineHCID 57900378HCID 57900378, compoundHCID 66899984HCID 66899984, compound

Product 1

HCID 57900151HCID 57900151, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-amine HCl salt (0.5 g, 1.16 mmol) in dried DCM (30 mL) was added DIPEA (0.61 mL, 3.48 mmol). The solution was stirred at 0° C. for 20 min and 2-chloro-acetyl chloride (0.2 g, 1.74 mmol) was added dropwise. The mixture was allowed to reach room temperature and stirred for a further 2 hours. The reaction solution was poured into ice water and extracted with EtOAc. The organics were combined, dried over Na2SO4 and evaporated in vacuum to afford the crude product (0.45 g, yield: 82%). 2-chloro-N-(2-(4-(2-chlorophenyl)-4H-1,2,4-triazol-3-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepin-8-yl)acetamide (0.2 g, 0.424 mmol) was mixed with HCl salt of NH(CH3)2 (0.172 g, 2.12 mmol) and NEt3 (0.3 mL, 2.12 mmol) in 15 mL of DCM. The solution was stirred at room temperature for 4 hours and quenched with ice water. Extraction with EtOAc and evaporation of the organics gave the crude product. It was purified by preparative TLC to afford 237 (40 mg, isolated yield: 20%). 1H NMR (DMSO-d6, 400 MHz): δ 9.81 (s, 1H), 8.81 (s, 1H), 7.79-7.38 (m, 7H), 6.55 (s, 1H), 4.16 (t, J=5.2 Hz, 2H), 3.02 (s, 3H), 2.96 (t, J=5.2 Hz, 2H), 2.21 (s, 6H). MS: (ESI+) 480.1

Workup

  1. customto reach room temperature
  2. stirringstirred for a further 2 hours
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. customevaporated in vacuum
  6. customto afford the crude product (0.45 g, yield: 82%)
  7. stirringThe solution was stirred at room temperature for 4 hours
  8. customquenched with ice water
  9. extractionExtraction
  10. customwith EtOAc and evaporation of the
  11. customorganics gave the crude product
  12. customIt was purified by preparative TLC

Sources & evidence

ORD record
ord-8a4510228c874d61953788e1ed57acc4
Source dataset
uspto-grants-2016_04
Patent number
US09309265B2

Reaction notes

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