Trifluoroacetic acid → (R)-6-nitro-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 510359Notes

Reaction equation

C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]2[C:17]3[N:18]=[CH:19][N:20]=[C:21]([NH2:22])[C:16]=3[C:15]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[CH:25][CH:24]=3)=[CH:14]2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.[N:43]([O-:45])=[O:44].[Na+]>>[N+:43]([C:14]1[N:13]([C@@H:10]2[CH2:11][CH2:12][NH:8][CH2:9]2)[C:17]2[N:18]=[CH:19][N:20]=[C:21]([NH2:22])[C:16]=2[C:15]=1[C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:27][CH:28]=1)([O-:45])=[O:44]

Participants

Reactant 3

HCID 6422Trifluoroacetic acid

HCID 23668193Sodium Nitrite

HCID 86719376(R)-tert-butyl-3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate

Product 1

HCID 86719407(R)-6-nitro-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amineYield 143.7%

Procedure

(R)-tert-Butyl 3-(4-amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)pyrrolidine-1-carboxylate (2) (400 mg, 0.85 mmol) was treated with TFA (6 mL). The resulting mixture was stirred at rt for 30 min, then NaNO2 (41 mg, 0.59 mmol) was added. After the stifling was continued for 1 hr, the reaction was concentrated under vacuum. DCM (10 mL×2) was added and concentrated to remove the residue TFA to afford (R)-6-nitro-5-(4-phenoxyphenyl)-7-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (160) (353 mg, quant. yield) as a yellow oil, which was used directly in next step without purification. LC-MS (ESI): m/z (M+1) 417.2.

Workup

waitAfter the stifling was continued for 1 hr
concentrationthe reaction was concentrated under vacuum
additionDCM (10 mL×2) was added
concentrationconcentrated
customto remove the residue TFA

Sources & evidence

ORD record: ord-34ff9a7deb4241b2b254b4b2bfcd00fe
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096604B2

Reaction notes

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