Formaldehyde → 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-2-methyl-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

HRID 627409Notes

Reaction equation

HRID 627409 reaction equation
[CH:1]1([N:8]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]5[C:29](=[O:30])[CH2:28][C@H:27]6[CH2:31][NH:32][CH2:33][C@H:26]6[CH2:25]5)=[CH:20][N:19]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]2[C:34]([N:36]([CH3:38])[CH3:37])=[O:35])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:39]=O.[Na]>C1COCC1>[CH:1]1([N:8]2[C:12]3[N:13]=[C:14]([NH:17][C:18]4[CH:23]=[CH:22][C:21]([N:24]5[C:29](=[O:30])[CH2:28][C@H:27]6[CH2:31][N:32]([CH3:39])[CH2:33][C@H:26]6[CH2:25]5)=[CH:20][N:19]=4)[N:15]=[CH:16][C:11]=3[CH:10]=[C:9]2[C:34]([N:36]([CH3:38])[CH3:37])=[O:35])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5360545SodiumHCID 673554517-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Product 1

HCID 673557607-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-2-methyl-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamideYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7aR)-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (from example 89, enantiomer-2) (66 mg, 0.128 mmol, 1 eq) in THF (2.0 mL) was added 37% aquous solution of formaldehyde (0.048 mL, 0.639 mmol, 5 eq). The reaction mixture was stirred at room temperature for 5 minutes. Solid sodium triacetoxyhydroborate (81 mg, 0.383 mmol, 3 eq was added into the mixture. The reaction was stirred for 10 more minutes and quenched with a drop of TEA and naturalized with amonia in methanol. The residue was concentrated under vacuum and purified by column chromatography (NH3/MeOH/CH2Cl2) to provide 7-cycloheptyl-N,N-dimethyl-2-(5-((3aS,7a R)-2-methyl-6-oxotetrahydro-1H-pyrrolo[3,4-c]pyridin-5(6H,7H,7aH)-yl)pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (67 mg) in quantitative yield. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (s, 1H), 8.63 (d, J=9.09 Hz, 1H), 8.27 (s, 1H), 8.24 (d, J=2.53 Hz, 1H), 7.67 (dd, J1=9.09, J2=2.53 Hz, 1H), 6.44 (s, 1H), 4.73 (s, 3H), 4.52 (m, 1H), 3.83 (dd, J1=13.14, J2=4.04 Hz, 1H), 3.65 (dd, J1=13.14, J2=4.04 Hz, 1H), 3.17 (s, 6H), 2.91-2.51 (m, 7H), 2.36 (m, 4H), 2.01 (m, 2H), 1.87 (m, 2H), 1.79-1.51 (m, 5H); HRMS m/z 531.3219 (M+H)+.

Workup

  1. stirringThe reaction was stirred for 10 more minutes
  2. customquenched with a drop of TEA and naturalized with amonia in methanol
  3. concentrationThe residue was concentrated under vacuum
  4. custompurified by column chromatography (NH3/MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-aab82f6f9aba4baf98dcaf04c1aac630
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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