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Ammonium Chloride → 4-[1-(2-aminopyrimidin-4-yl)-2-(oxetan-3-yloxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

HRID 1398686
Notes
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Reaction equation

HRID 1398686 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[C:9]([O:11][CH:12]3[CH2:15][O:14][CH2:13]3)[N:8]([C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH2:22])[N:17]=3)[C:7]=2[CH:23]=1)#[CH:2].C([N-]C(C)C)(C)C.[Li+].[N:32]1[CH:37]=[CH:36][CH:35]=[N:34][C:33]=1[C:38](=[O:40])[CH3:39].[Cl-].[NH4+]>C1COCC1>[NH2:22][C:18]1[N:17]=[C:16]([N:8]2[C:7]3[CH:23]=[C:3]([C:1]#[C:2][C:38]([C:33]4[N:34]=[CH:35][CH:36]=[CH:37][N:32]=4)([OH:40])[CH3:39])[CH:4]=[CH:5][C:6]=3[N:10]=[C:9]2[O:11][CH:12]2[CH2:13][O:14][CH2:15]2)[CH:21]=[CH:20][N:19]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 116079091-(Pyrimidin-2-yl)ethan-1-oneHCID 866696124-[6-ethynyl-2-(oxetan-3-yloxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine

Product 1

HCID 681817484-[1-(2-aminopyrimidin-4-yl)-2-(oxetan-3-yloxy)-1H-1,3-benzodiazol-6-yl]-2-(pyrimidin-2-yl)but-3-yn-2-ol

Reagents, catalysts & solvents

1
HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 4-[6-ethynyl-2-(oxetan-3-yloxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (270 mg, 0.88 mmol) in dry THF (5 mL) at −78° C. was introduced lithium diisopropylamide (1.10 mL of a 2M solution in THF, 2.20 mmol). After 15 minutes, 1-pyrimidin-2-yl-ethanone (107 mg, 0.88 mmol) was added and the reaction mixture maintained at −78° C. for 15 minutes. Following 2 hr at RT, saturated aqueous ammonium chloride (0.5 ml) was added and the solution concentrated in vacuo. The residue was dissolved in DCM (10 mL), washed with water (2 mL), dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by column chromatography (Biotage, DCM containing a 0-12% gradient of methanol) furnished the title compound as a yellow solid: 1H NMR (500 MHz, DMSO) delta 1.90 (3H, s), 4.78 (2H, dd, J=7.8, 4.9 Hz), 4.98 (2H, t, J=7.1 Hz), 5.87-5.80 (1H, m), 6.16 (1 H, s), 7.11 (1H, d, J=5.5 Hz), 7.14 (2H, s), 7.25 (1H, dd, J=8.2, 1.2 Hz), 7.45 (1H, d, J=8.2 Hz), 7.52 (1H, t, J=4.8 Hz), 8.16 (1H, s), 8.44 (1H, d, J=5.5 Hz), 8.91 (2H, d, J=4.8 Hz); LC-MS: m/z=+430.05 (M+H)+.

Workup

  1. waitFollowing 2 hr at RT
  2. concentrationthe solution concentrated in vacuo
  3. dissolutionThe residue was dissolved in DCM (10 mL)
  4. washwashed with water (2 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by column chromatography (Biotage, DCM containing a 0-12% gradient of methanol)

Sources & evidence

ORD record
ord-97e5158e5a1047079a15c4f8c35795c9
Source dataset
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08901313B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes