Triphenylphosphine → 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine

HRID 897435Notes

Reaction equation

HRID 897435 reaction equation
[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[NH:4][N:3]=1.[O:12]1[C:16]2([CH2:21][CH2:20][CH:19](O)[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[O:12]1[C:16]2([CH2:21][CH2:20][CH:19]([N:4]3[C:5]4=[N:6][CH:7]=[N:8][C:9]([NH2:11])=[C:10]4[C:2]([I:1])=[N:3]3)[CH2:18][CH2:17]2)[O:15][CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 5673521,4-Dioxaspiro(4.5)decan-8-ol2×HCID 178508725HCID 178508725, compound

Product 1

HCID 223470211-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamineYield 54.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

3-Iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (Intermediate LA) (11 g, 0.042 mol) was suspended in tetrahydrofuran (500 mL) at room temperature under a nitrogen atmosphere. A solution of 1,4-dioxaspiro[4.5]decan-8-ol (Intermediate M) (19.98 g, 0.126 mol) in tetrahydrofuran (50 mL) and subsequently triphenylphosphine (22.1 g, 0.084 mol ) was added to the suspension. The suspension was cooled to 0° C. and then diethyl azodicarboxylate (14.67 g, 0.084 mol) was added slowly. After stirring the reaction mixture at 0° C. for 15 min, it was allowed to warm to room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (300-400 mL) and allowed to stand overnight. A precipitate formed which was collected by filtration, washed with ethyl acetate, and dried on the lyophilizer to give 1-(1,4-dioxaspiro[4.5]dec-8-yl)-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine as a pale yellow solid (54%, 9.12 g, 0.023 mol): 1H NMR (DMSO-d6, 400 MHz) 8.19 (s, 1H), 4.70 (m, 1H), 3.90 (m, 4H), 2.13 (m, 2H), 1.74 (m, 6H). TLC (dichloromethane/methanol=9:1) Rf 0.61.

Workup

  1. temperatureto warm to room temperature for 1 hour
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (300-400 mL)
  4. waitto stand overnight
  5. customA precipitate formed which
  6. filtrationwas collected by filtration
  7. washwashed with ethyl acetate
  8. customdried on the lyophilizer

Sources & evidence

ORD record
ord-048c8e29a01742a09c2a2330da948760
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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