Water → HCID 58529843, compound

HRID 1972778Notes

Reaction equation

HRID 1972778 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:17]=3)[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14]O)[N:6]2[N:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:50].O>O1CCCC1>[CH2:23]([O:22][C:18]1[CH:17]=[C:16]([C:8]2[CH:9]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][Br:50])[N:6]3[C:7]=2[C:2]([NH2:1])=[N:3][CH:4]=[N:5]3)[CH:21]=[CH:20][CH:19]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 58529551HCID 58529551, compound

Product 1

HCID 58529843HCID 58529843, compoundYield 85.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 4{4-amino-5-[3-(benzyloxy)phenyl]pyrrolo[2,1-f][1,2,4]triazin-7-yl}butan-1-ol (489 mg, 1.26 mmol) and triphenylphosphine (495 mg, 1.89 mmol) in tetrahydrofuran (8 mL) was added carbon tetrabromide (501 mg, 1.51 mmol). The reaction was stirred (0° C.) for 2 h and was then warmed to rt and stirred an additional 17 h. Water (25 mL) was added and the mixture was extracted with ethyl acetate (2×20 mL). The combined organics were washed with brine, dried (Na2SO4) and evaporated. The crude material was purified via ISCO® chromatography using a gradient of 25 to 50% ethyl acetate in hexanes to afford 484 mg (85%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ7.88 (s, 1 H), 7.46-7.42 (m, 2 H), 7.41-7.28 (m, 4 H), 7.08-7.05 (m, 1 H), 7.03-6.97 (m, 2 H), 6.57 (s, 1 H), 5.14 (s, 2 H), 3.57 (t, 2 H), 2.90 (t, 2 H), 1.92-1.77 (m, 4 H); ES-MS m/z 451.1 [M+H]+, HPLC RT (min) 3.22.

Workup

  1. temperaturewas then warmed to rt
  2. stirringstirred an additional 17 h
  3. extractionthe mixture was extracted with ethyl acetate (2×20 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customThe crude material was purified via ISCO® chromatography

Sources & evidence

ORD record
ord-dbacce410d704bfe8e1b55d856a9000f
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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