Dichloromethane → Hydrochloric Acid

HRID 1410000Notes

Reaction equation

HRID 1410000 reaction equation
C(OC([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15](=[O:42])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[N:23]=[C:24]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34]([O:40][CH3:41])[CH:33]=4)[C:25]4[N:30]=[CH:29][S:28][C:26]=4[N:27]=3)[CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:51]>>[N:11]1([C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]3[N:23]=[C:24]([NH:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[C:34]([O:40][CH3:41])[CH:33]=4)[C:25]4[N:30]=[CH:29][S:28][C:26]=4[N:27]=3)[CH:17]=2)=[O:42])[CH2:12][CH2:13][CH2:14][NH:8][CH2:9][CH2:10]1.[ClH:51]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 683794114-{3-[7-(3,4-Dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl ester

Product 2

HCID 313Hydrochloric AcidYield 30.2%HCID 66551344[1,4]Diazepan-1-yl-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-phenyl}-methanone

Procedure

To a stirred solution of 4-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl ester (130 mg, 0.22 mmol) in 10 mL of CH2Cl2 was added slowly CF3COOH (4 mL) at room temperature. Then the mixture was stirred at room temperature for 16 hours. The solvent was evaporated and the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.), then 1M HCl (0.5 mL) was added and stirred, then solvents were removed under reduced pressure to give [1,4]diazepan-1-yl-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-phenyl}-methanone as HCl salt (35 mg, 30.2%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.18 (s, 1H), 9.38 (s, 1H), 9.05 (brs, 2H), 8.46-8.44 (m, 2H), 7.86 (s, 1H), 7.60-7.59 (m, 2H), 7.42 (dd, 1H, J1=8.7 Hz, J2=2.7 Hz), 6.99 (d, 1H, J=8.7 Hz), 3.85 (brs, 2H), 3.80 (s, 3H), 3.77 (s, 3H), 3.44 (brs, 2H), 3.30 (brs, 2H), 3.20 (brs, 2H), 2.02-1.96 (m, 2H). LC-MS: 491.2 [M+H]+, tR=1.51 min. HPLC: 99.24% at 214 nm, 98.23% at 254 nm, tR=4.65 min.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  3. wait20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.
  4. addition), then 1M HCl (0.5 mL) was added
  5. stirringstirred
  6. customsolvents were removed under reduced pressure

Sources & evidence

ORD record
ord-f3391fc05f2d47e39bbf677270de83b2
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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