Dimethylamine → 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-dimethylaminomethyl-cyclopropyl)-isoxazol-3-yl]-amide

HRID 884626Notes

Reaction equation

HRID 884626 reaction equation
C(OC([N:8]1[CH2:16][C:15]2[C:14]([O:17][C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23]([C:27](=[O:39])[NH:28][C:29]3[CH:33]=[C:32]([C:34]5([CH:37]=O)[CH2:36][CH2:35]5)[O:31][N:30]=3)[CH:22]=[CH:21]4)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)=O)(C)(C)C.[CH3:40][NH:41][CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(C(F)(F)F)=O>ClCCCl.[Cl-].[Na+].O.C(Cl)Cl>[CH3:40][N:41]([CH2:37][C:34]1([C:32]2[O:31][N:30]=[C:29]([NH:28][C:27]([N:23]3[C:24]4[C:20](=[CH:19][C:18]([O:17][C:14]5[C:15]6[CH2:16][NH:8][CH2:9][C:10]=6[N:11]=[CH:12][N:13]=5)=[CH:26][CH:25]=4)[CH:21]=[CH:22]3)=[O:39])[CH:33]=2)[CH2:35][CH2:36]1)[CH3:42]

Participants

8

Reactant 4

HCID 674DimethylamineHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 593941044-{1-[5-(1-Formyl-cyclopropyl)-isoxazol-3-ylcarbamoyl]-1H-indol-5-yloxy}-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester

Product 1

HCID 593945735-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-dimethylaminomethyl-cyclopropyl)-isoxazol-3-yl]-amide

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of 4-{1-[5-(1-formyl-cyclopropyl)-isoxazol-3-ylcarbamoyl]-1H-indol-5-yloxy}-5,7-dihydro-pyrrolo[3,4-d]pyrimidine-6-carboxylic acid tert-butyl ester (120 mg, 0.226 mmol) in DCE (2 ml), dimethylamine (0.34 mL, 0.679 mmol) and sodium triacetoxyborohydride (192 mg, 0.905 mmol) are added. After 2 h the reaction is complete, brine is added and the product is extracted with EtOAc. The organics are dried and evaporated to give the crude product. The mixture is diluted with DCM (10 mL) and then TFA (10 ml, 130 mmol) is added. After 10 minutes the volatiles are removed in vacuo. The product is dissolved in EtOAc and then NH4OH is added. The organics are removed and the crude product separated via FCC eluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1) to give 5-(6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid [5-(1-dimethylaminomethyl-cyclopropyl)-isoxazol-3-yl]-amide. MS (ESI) m/z 460.9 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.55 (s, 1H) 8.29 (d, J=8.84 Hz, 1H) 8.16 (d, J=3.79 Hz, 1H) 7.47 (d, J=2.27 Hz, 1H) 7.16 (s, 1H) 6.82 (s, 1H) 6.75 (d, J=4.04 Hz, 1H) 4.06-4.15 (m, 1H) 2.57 (s, 2 H) 2.20 (s, 6H) 1.17 (d, J=2.27 Hz, 2H) 0.93 (d, J=2.27 Hz, 2H).

Workup

  1. extractionthe product is extracted with EtOAc
  2. customThe organics are dried
  3. customevaporated
  4. customto give the crude product
  5. customAfter 10 minutes the volatiles are removed in vacuo
  6. dissolutionThe product is dissolved in EtOAc
  7. additionNH4OH is added
  8. customThe organics are removed
  9. customthe crude product separated via FCC
  10. washeluting with DCM:MeOH:NH4OH (100:0:0 to 92:7:1)

Sources & evidence

ORD record
ord-500cf3e050f9455d8407273042a25618
Source dataset
uspto-grants-2012_08
Patent number
US08242125B2

Reaction notes

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