Ammonia → HCID 9922078, compound

HRID 1835178Notes

Reaction equation

HRID 1835178 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21]O)[CH:11]=3)=[CH:9][C:2]=12.C(Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH3:47]>ClCCl>[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21][NH2:47])[CH:11]=3)=[CH:9][C:2]=12

Participants

6

Reactant 4

HCID 222Ammonia2×HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 9922101HCID 9922101, compound

Product 1

HCID 9922078HCID 9922078, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol [12 g, Example 2(a)] and carbon tetrabromide (19.1 g) in dichloromethane (300 mL) at ambient temperature was treated with a solution of triphenylphosphine (12.9 g) in dichloromethane (100 mL) over 5 minutes. After stirring at ambient temperature for 3 hour the reaction mixture was filtered and the solid was washed with sparing amounts of dichloromethane. The filtrate and washings were evaporated to yield a brown gum, which was mixed with liquid ammonia (ca 80 mL) in a sealed pressure vessel and allowed to stir at ambient temperature for 18 hours. The vessel was then cooled to −78° C. and then cautiously vented. The ammonia was allowed to evaporate and the residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane, methanol and concentrated ammonia (900:100:7, v/v/v) to give the title compound as a yellow solid (3 g), m.p. 170° C. 1H NMR [(CD3)2SO]: δ 8.28 (1H, d, J=2.7 Hz); 8.18 (1H, s); 8.10, 7.64 (each 1H, d, J=7.7 Hz); 8.09 (1H, d, J=2.7 Hz); 7.29, 7.23 (each 1H, td, J=7.1 and 1.0 Hz); 6.97 (1H, s); 4.32 (2H, t, J=7.0 Hz); 2.57 (2H, t, J=6.5 Hz); 1.89 (2H, quintet, J=6.4 Hz).

Workup

  1. filtrationwas filtered
  2. washthe solid was washed with sparing amounts of dichloromethane
  3. customThe filtrate and washings were evaporated
  4. customto yield a brown gum, which
  5. stirringto stir at ambient temperature for 18 hours
  6. temperatureThe vessel was then cooled to −78° C.
  7. customto evaporate
  8. additionthe residue was subjected to flash chromatography on silica eluting with a mixture of dichloromethane, methanol and concentrated ammonia (900:100:7, v/v/v)

Sources & evidence

ORD record
ord-4a866e72004543a184dca177ee2fd8ae
Source dataset
uspto-grants-2004_08
Patent number
US06770643B2

Reaction notes

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