Hydrochloric Acid → (R)-N-(1-(5-Chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)acrylamide

HRID 577704Notes

Reaction equation

HRID 577704 reaction equation
Cl.O1CCO[CH2:4][CH2:3]1.[Cl:8][C:9]1[C:17]2[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([NH:24][C:25](=O)[O:26]C(C)(C)C)[CH2:19]3)=[N:15][C:14]([NH:32][C:33]3[CH:34]=[N:35][N:36]([CH3:38])[CH:37]=3)=[N:13][C:12]=2[NH:11][CH:10]=1.C(Cl)(=O)C=C>CO>[Cl:8][C:9]1[C:17]2[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][C@@H:20]([NH:24][C:25](=[O:26])[CH:3]=[CH2:4])[CH2:19]3)=[N:15][C:14]([NH:32][C:33]3[CH:34]=[N:35][N:36]([CH3:38])[CH:37]=3)=[N:13][C:12]=2[NH:11][CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13140Acryloyl chlorideHCID 312751,4-DioxaneHCID 86679648tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate

Product 1

HCID 86679649(R)-N-(1-(5-Chloro-2-((1-methyl-1H-pyrazol-4-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)acrylamideYield 81.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 4 M HCl in 1,4-dioxane (0.31 mL, 1.3 mmol) was added to a solution of tert-butyl (1-{5-chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-yl)carbamate (56 mg, 0.12 mmol) in methanol (1.3 mL). After 24 hrs, the mixture was concentrated to dryness by rotary evaporation. The resulting residue was suspended in EtOAc (2.5 mL) and saturated aqueous sodium bicarcarbonate solution (1.3 mL). Acryloyl chloride (13 μL, 0.16 mmol) was added and the mixture was stirred for 1 hr. The organic layer was separated, dried over MgSO4 and evaporated to give the title compound (39 mg, 69% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.40 (br. s., 1H), 8.76 (s, 1H), 8.14 (d, J=7.82 Hz, 1H), 7.83 (s, 1H), 7.47 (s, 1H), 7.05 (d, J=2.45 Hz, 1H), 6.19-6.31 (m, 1H), 6.07-6.16 (m, 1H), 5.60 (dd, J=10.03, 2.45 Hz, 1H), 4.13 (d, J=12.23 Hz, 1H), 4.03 (d, J=12.72 Hz, 1H), 3.85-3.98 (m, 1H), 3.77 (s, 3H), 2.96 (t, J=11.25 Hz, 1H), 2.80 (t, J=11.13 Hz, 1H), 1.89-2.00 (m, 1H), 1.79-1.88 (m, 1H), 1.67-1.79 (m, 1H), 1.40-1.57 (m, 1H). m/z (APCI+) for C18H21ClN8O 401.2 (M+H)+.

Workup

  1. concentrationthe mixture was concentrated to dryness by rotary evaporation
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated

Sources & evidence

ORD record
ord-070eb09bc6f348c9b2fdca024472c29a
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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